A method for ruthenium-catalyzed synthesis of acyloxy 2-benzoylpyridine compounds

Abstract

The application discloses a method for synthesizing acyloxy 2-benzoyl pyridine compounds under catalysis of ruthenium, relates to the technical field of compound synthesis, and uses 2-benzoyl pyridine compounds and sodium carboxylate compounds as substrates to synthesize acyloxy 2-benzoyl pyridine compounds under the action of a ruthenium catalyst. The application solves the problems of harsh traditional reaction conditions, complex operation, substrate limitation and complicated steps, and greatly enriches the structural diversity of the compounds.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of organic synthesis, in particular to a method for synthesizing acyloxy 2-benzoyl pyridine compounds catalyzed by ruthenium. BACKGROUND

[0002] At present, transition metal-catalyzed C-H functionalization is considered to be one of the reliable strategies for synthesizing useful and complex molecules from structurally simple compounds. Aryl ester compounds are widely present in natural products, drugs, bioactive compounds, and spices. The traditional synthesis method of such compounds relies on the cross-coupling reaction of aromatic alcohol or aryl silicon with carbonyl compounds, which has harsh reaction conditions and poor functional group tolerance, and the diversity of products is limited. People have been exploring new methods to build C-O bonds. So far, C-H acyloxylation is one of the most effective strategies for introducing oxygen functional groups in organic compounds.

[0003] Various transition metal catalysts have been reported for C-H acyloxylation. Among them, Ru(II)-catalyzed C-H acyloxylation with carboxylic acids has been widely studied. Jeganmohan reported Ru(II)-catalyzed C-H benzyloxylation of acetanilides and N-alkylbenzamides with aromatic carboxylic acids in 2013 and 2014, respectively. Ackermann subsequently reported Ru(II)-catalyzed C-H acyloxylation of 2-pyridyloxy arenes with carboxylic acids. Since then, various substrates such as carbazoles, benzamides, indolines, and azo arenes have been used in Ru(II)-catalyzed C-H acyloxylation.

[0004] Although great progress has been made in transition metal-catalyzed C-H acyloxylation in recent years, most of them use carboxylic acids as acyloxy sources, and the diversity of substrates is limited. Sodium salts of acid drugs are widely used in drug development due to their excellent solubility, good pharmacokinetic properties, and chemical stability. Therefore, it is of great significance to develop a Ru(II)-catalyzed C-H acyloxylation reaction using sodium salts as acyloxy sources, which not only expands the diversity of aromatic ester compounds but also applies to the "Late-Stage" of drugs, providing a method for drug development. SUMMARY

[0005] The purpose of the present application is to provide a method for synthesizing acyloxy 2-benzoyl pyridine compounds catalyzed by ruthenium, which uses 2-benzoyl pyridine compounds and sodium carboxylate compounds as raw materials to synthesize acyloxy 2-benzoyl pyridine compounds (Formula I).

[0006] The technical scheme adopted by the present application is:

[0007] A method for ruthenium-catalyzed synthesis of acyloxy 2-benzoylpyridine compounds, comprising the following steps: mixing 2-benzoylpyridine compounds, sodium carboxylate compounds, [RuCl2(p-cymene)]2, AgSbF6, Ag2CO3, and reacting in an organic solvent for 12-24 hours; after the reaction is completed, using water and ethyl acetate for extraction, combining the organic layers, drying, filtering, concentrating, and separating and purifying to obtain a compound of formula I, and the reaction general formula is as follows:

[0008]

[0009] R is selected from hydrogen, C1-C 30 alkyl, C3-C 11 cycloalkyl, aryl, arylhetero group, adamantyl, C1-C 30 alkenyl, terpenoid group, steroid group;

[0010] each R 1 is independently selected from hydrogen, C1-C5 alkyl, C1-C5 alkoxy, aryl, halogen, ester group; two adjacent R 1 may form, together with the atoms to which they are attached, a five- to six-membered saturated or unsaturated aromatic or aromatic heterocyclic ring;

[0011] each R 2 is independently selected from hydrogen, C1-C5 alkyl, halogen; two adjacent R 2 may form, together with the atoms to which they are attached, a five- to six-membered saturated or unsaturated aromatic or aromatic heterocyclic ring;

[0012] m and s are independently selected from 1, 2 or 3.

[0013] In the present application, the addition order of the 2-benzoylpyridine compounds, sodium carboxylate compounds, [RuCl2(p-cymene)]2, AgSbF6 and Ag2CO3 is not limited.

[0014] In some embodiments, the 2-benzoylpyridine compounds and sodium carboxylate compounds are mixed first, and then [RuCl2(p-cymene)]2, AgSbF6 and Ag2CO3 are sequentially added.

[0015] Further, the molar ratio of the 2-benzoylpyridine compounds to the sodium carboxylate compounds is (0.1-0.5):(0.2-1.0).

[0016] In some embodiments, the molar ratio of the 2-benzoylpyridine compounds to the sodium carboxylate compounds is 0.2:0.4.

[0017] In some embodiments, the molar ratio of the 2-benzoylpyridine compounds to the sodium carboxylate compounds is 0.2:0.3.

[0018] Further, the molar ratio of the 2-benzoylpyridine compound to AgSbF6 is (0.1-0.5):(0.04-0.1).

[0019] Further, the equivalent ratio of the sodium carboxylate compound to Ag2CO3 is (1-2):(1-2), preferably 1:1.

[0020] Further, the molar ratio of the sodium carboxylate compound to [RuCl2(p-cymene)]2 is (0.2-1.0):(0.01-0.06).

[0021] In the present application, the organic solvent is selected from one or more of PhCF3, DMF, CH3CN or DCE, preferably DCE.

[0022] In the present application, the extraction times of water and ethyl acetate are 3-5 times, preferably 3 times.

[0023] In the present application, the purification is all by silica gel column chromatography, and the eluent ratio is petroleum ether: ethyl acetate = 10:1-5:1.

[0024] In the present application, the reaction temperature is 100-150°C, preferably 120°C.

[0025] In some embodiments, the reaction formula of the ruthenium catalyzed synthesis of acyloxy 2-benzoylpyridine compounds is as follows:

[0026]

[0027] The present application also provides acyloxy 2-benzoylpyridine compounds, the structural formula of which is as follows:

[0028]

[0029] Further, R is selected from hydrogen, C1-C 20 alkyl, C3-C6 cycloalkyl, aryl, arylhetero group, adamantyl, C1-C 20 alkenyl, terpenoid group, steroid group; each R 1 is independently selected from hydrogen, C1-C5 alkyl, C1-C5 alkoxy, aryl, halogen, ester group; two adjacent R 1 may form, together with the atom to which they are attached, a five- to six-membered saturated or unsaturated aromatic or aromatic heterocyclic ring; each R 2 is independently selected from hydrogen, C1-C3 alkyl, halogen; two adjacent R 2 may form, together with the atom to which they are attached, a five- to six-membered saturated or unsaturated aromatic or aromatic heterocyclic ring;

[0030] Further, m and s are independently selected from 1 or 2.

[0031] In the present application, the acyloxy 2-benzoyl pyridine compounds are selected from the following compounds:

[0032]

[0033]

[0034]

[0035] The 35 compounds prepared here are numbered according to different categories, and the number is the content in the brackets after the structural formula. This number is only for subsequent description.

[0036] Unless otherwise indicated, the following terms used in the present application are intended to have the following definitions. A particular term should not be considered unclear if it is not specifically defined, but should be understood according to its ordinary meaning.

[0037] When any variable (for example, R 1 ) appears more than once in a compound or a structure, each occurrence of that variable is independent of the others. Thus, for example, if a group is substituted with 0-2 R 1 , the group can optionally be substituted with up to two R 1 , and each occurrence of R is independently selected. In addition, combinations of substituents and / or variables are permissible only if such combinations result in stable compounds.

[0038] The aforementioned aryl is an all-carbon monocyclic or fused ring poly cyclic aromatic group having a conjugated pi-electron system; aryl groups can have from 6 to 10 carbon atoms in one or more rings. Most commonly, aryl groups have 6 carbon atoms in the ring. For example, C6-C 10 Aryl is an aromatic group containing 6 to 10 carbon atoms, such as phenyl or naphthyl.

[0039] Advantages of the present application: the present application uses 2-benzoyl pyridine compounds and sodium carboxylate compounds as substrates, which have good solubility and stability, and under the action of ruthenium catalyst, acyloxy 2-benzoyl pyridine compounds are synthesized; the present application solves the problems of harsh reaction conditions, complex operation, limited substrates and tedious steps of traditional reactions, and greatly enriches the structural diversity of such compounds.

[0040] The abbreviations in the present application have the following meanings:

[0041] PhCF3 represents trifluorotoluene;

[0042] DMF represents dimethylformamide;

[0043] CH3CN represents acetonitrile;

[0044] DCE represents dichloroethane. DETAILED DESCRIPTION

[0045] In order to make the objectives, technical solutions and advantages of the present application more apparent, the present application will be further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and should not be used to limit the present application. In addition, if not specifically stated, all reagents used in the following examples are commercially available or can be synthesized according to the methods described herein or known methods, and the reaction conditions not listed are also readily available to those skilled in the art.

[0046] The reaction general formula for generating acyloxy 2-benzoyl pyridine compounds (Formula I) in the present application is as follows:

[0047]

[0048] The synthesis of specific Formula I compounds is described with reference to the following examples.

[0049] Example 1 Synthesis of acyloxy 2-benzoyl pyridine compounds of the present application:

[0050] (1) 3-methyl-2-picolinoylphenyl pivalate (3aa): yield 83%

[0051] In a reaction tube, 2-(2-methylbenzoyl)pyridine (39.7 mg, 0.20 mmol), sodium pivalate (49.6 mg, 0.40 mmol), [Ru(p-cymene)Cl2]2(6.1 mg, 0.01 mmol), AgSbF6(27.4 mg, 0.08 mmol), Ag2CO3(110.3 mg, 0.4 mmol) were added, dry dichloroethane (1 mL) was added, and the mixture was reacted at 120°C for 12 h to obtain a liquid mixture. After the reaction was completed, water was added, and ethyl acetate was extracted three times, the organic layers were combined, the organic layer was dried over anhydrous Na2SO4, filtered, concentrated, and separated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1-5 / 1) to obtain 3aa (49.4 mg, 83%).

[0052]

[0053] 1H NMR (600 MHz, CDC13) δ = 8.72 - 8.68 (m, 1H), 8.11 - 8.10 (m, 1H), 8.89 - 8.86 (m, 1H), 7.47 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.35 - 7.38 (m, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.04 (d, J = 8.2 Hz, 1H), 2.24 (s, 3H), 0.95 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 195.33, 174.78, 152.72, 148.84, 147.18, 136.28, 135.92, 130.93, 128.94, 126.51, 126.15, 122.18, 118.63, 37.82, 25.60, 18.36. HR-MS (ESI) m / z calcd for: C 18 H 19 NO3Na + [M+Na] + 320.1257, found 320.1260.

[0054] Example 2

[0055] According to the aforementioned synthetic reaction conditions of general formula, changing the 2-benzoylpyridine compound and sodium carboxylate compound substrates, the following acyloxy 2-benzoylpyridine compounds can be obtained:

[0056] (2) 3-methyl-2-picolinoylphenyl acetate (3ab): yield 67%

[0057]

[0058] 1 H NMR (600 MHz, CDC13) δ = 8.72 - 8.68 (m, 1H), 8.11 - 8.10 (m, 1H), 8.89 - 8.86 (m, 1H), 7.47 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.35 - 7.38 (m, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.04 (d, J = 8.2 Hz, 1H), 2.24 (s, 3H), 0.95 (s, 9H). 13C NMR (150 MHz, CDC13) δ = 164.5, 158.1, 150.4, 148.0, 137.4, 133.8, 133.2, 131.2, 129.5, 129.3, 128.2, 127.4, 126.3, 126.0, 122.3, 109.6, 55.7, 39.7, 29.4. HR-MS (ESI) m / z calcd for: C 15 H 14 NO3 + [M+H] + 256.0968, found 256.0971.

[0059] (3) 3-methyl-2-picolinoylphenyl butyrate (3ac): yield 78%

[0060]

[0061] 1 H NMR (600 MHz, CDC13) δ = 8.72 - 8.64 (m, 1H), 8.09 (d, J = 7.2 Hz, 1H), 7.90 - 7.88 (m, 1H), 7.49 - 7.45 (m, 1H), 7.40 - 7.35 (m, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 9.3 Hz, 1H), 2.24 (s, 3H), 2.04 (t, J = 6.1 Hz, 2H), 1.46 - 1.39 (m, 2H), 0.79 (t, J = 7.6 Hz, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.51, 171.13, 154.10, 149.94, 148.10, 137.63, 137.09, 131.93, 130.22, 127.86, 127.17, 123.09, 120.06, 35.81, 19.59, 18.04, 13.56. HR-MS (ESI) m / z calcd for: C 17 H 18 NO3 + [M+H] + 284.1281, found 284.1283.

[0062] (4) 3-methyl-2-picolinoylphenyl hexanoate (3ad): yield 80%

[0063]

[0064] 1 1H NMR (600 MHz, CDCl3) δ = 8.71–8.67 (m, 1H), 8.09 (d, J = 7.8 Hz, 1H), 7.90–7.88 (m, 1H), 7.50–7.45 (m, 1H), 7.41–7.35 (m, 1H), 7.15 (d, J = 5.2 Hz, 1H), 7.07 (d, J = 5.6 Hz, 1H), 2.25 (s, 3H), 2.04 (t, J = 7.3 Hz, 2H), 1.40–1.34 (m, 2H), 1.23–1.17 (m, 2H), 1.17–1.11 (m, 2H), 0.83 (t, J = 7.9 Hz, 3H). 13 13C NMR (150 MHz, CDCl3) δ = 196.50, 171.28, 154.10, 149.93, 148.12, 137.62, 137.08, 131.92, 130.21, 127.85, 127.16, 123.09, 120.05, 33.97, 31.14, 24.20, 22.28, 19.58, 13.93. HR-MS (ESI) m / z calcd for: C 19 H 22 NO3 + [M + H] + 312.1594, found 312.1599.

[0065] (5) 3-methyl-2-picolinoylphenyl decanoate (3ae:) The yield was 79%.

[0066]

[0067] 1 1H NMR (600 MHz, CDCl3) δ = 7.82 (d, J = 3.7 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.04–7.00 (m, 1H), 6.60 (ddd, J = 7.7, 4.7, 1.3 Hz, 1H), 6.52–6.49 (m, 1H), 6.28 (d, J = 7.7 Hz, 1H), 6.20 (d, J = 8.2 Hz, 1H), 1.38 (s, 3H), 1.19–1.16 (m, 2H), 0.51–0.47 (m, 2H), 0.44–0.38 (m, 4H), 0.38–0.35 (m, 4H), 0.31–0.27 (m, 4H), 0.01 (t, J = 7.1 Hz, 3H).<00> 13C NMR (150 MHz, CDC13) δ = 196.39, 171.19, 154.06, 149.85, 148.07, 137.55, 136.97, 131.84, 130.13, 127.76, 127.04, 123.01, 119.96, 33.94, 31.86, 29.34, 29.24, 29.16, 28.93, 24.45, 22.67, 19.50, 14.12. HR-MS (ESI) m / z calcd for: C 23 H 30 NO3 + [M+H] + 368.2220, found 368.2221.

[0068] (6) 3-methyl-2-picolinoylphenyl heptadecanoate (3af): yield 65%

[0069]

[0070] 1 H NMR (600 MHz, CDC13) δ = 8.69 (d, J = 4.8 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.91 - 7.86 (m, 1H), 7.46 (dd, 1H), 7.39 - 7.34 (m, 1H), 7.15 (d, J = 7.7 Hz, 1H), 7.07 (d, J = 8.2 Hz, 1H), 2.24 (s, 3H), 2.04 (t, J = 7.6 Hz, 2H), 1.38 - 1.34 (m, 2H), 1.28 - 1.22 (m, 21H), 1.17 - 1.12 (m, 4H), 0.88 (t, J = 6.9 Hz, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.38, 171.19, 154.07, 149.84, 148.07, 137.55, 136.97, 131.85, 130.12, 127.76, 127.04, 123.00, 119.96, 33.94, 31.94, 29.71, 29.67, 29.59, 29.40, 29.37, 29.17, 28.94, 24.46, 22.70, 19.49, 14.13. HR-MS (ESI) m / z calcd for:

[0071] C 31 H 45 NO3Na + [M+Na] +502.3291, found 502.3292.

[0072] (7) N-(5-fluoro-2-(phenylselanyl)phenethyl)picolinamide (3ag): yield 84%

[0073]

[0074] 1 H NMR (600 MHz, CDC13) δ = 8.73 - 8.69 (m, 1H), 8.09 (d, J = 7.8 Hz, 1H), 7.90 - 7.85 (m, 1H), 7.47 (ddd, J = 7.6, 4.7, 1.3 Hz, 1H), 7.38 - 7.33 (m, 1H), 7.13 (d, J = 7.7 Hz, 1H), 7.04 (d, J = 8.2 Hz, 1H), 2.24 (s, 3H), 1.89 - 1.85 (m, 3H), 1.65 - 1.61 (m, 3H), 1.59 - 1.57 (m, 6H), 1.55 - 1.51 (m, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.40, 174.96, 153.92, 149.98, 148.34, 137.43, 136.98, 131.96, 130.06, 127.56, 127.18, 123.42, 119.81, 40.84, 38.25, 36.32, 27.75, 19.48. HR-MS (ESI) m / z calcd for: C 24 H 26 NO3 + [M+H] + 376.1907, found 376.1912.

[0075] (8) 3-methyl-2-picolinoylphenyl cyclopropanecarboxylate (3ah): yield 71%

[0076]

[0077] 1H NMR (600 MHz, CDC13) δ = 8.71 - 8.67 (m, 1H), 8.11 - 8.06 (m, 1H), 7.92 - 7.86 (m, 1H), 7.50 - 7.45 (m, 1H), 7.39 - 7.34 (m, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H), 2.26 (s, 3H), 1.37 - 1.31 (m, 1H), 0.80 - 0.76 (m, 2H), 0.72 - 0.66 (m, 2H). 13 C NMR (150 MHz, CDC13) δ = 196.37, 172.25, 154.09, 149.81, 148.08, 137.65, 136.96, 131.74, 130.16, 127.78, 127.01, 123.03, 119.98, 19.49, 12.58, 8.78. HR-MS (ESI) m / z calcd for: C 17 H 16 NO3 + [M+H] + 282.1125, found 282.1128.

[0078] (9) 3-methyl-2-picolinoylphenyl cyclopentanecarboxylate (3ai): yield 81%

[0079]

[0080] 1 H NMR (600 MHz, CDC13) δ = 8.72 - 8.67 (m, 1H), 8.09 (d, J = 7.6 Hz, 1H), 7.91 - 7.86 (m, 1H), 7.49 - 7.45 (m, 1H), 7.40 - 7.34 (m, 1H), 7.14 (d, J = 6.7 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 2.54 - 2.45 (m, 1H), 2.24 (s, 3H), 1.65 - 1.59 (m, 2H), 1.55 - 1.47 (m, 4H), 1.47 - 1.39 (m, 2H). 13C NMR (150 MHz, CDC13) δ = 196.43, 174.05, 153.86, 149.87, 148.08, 137.38, 136.98, 131.91, 130.04, 127.62, 127.12, 123.11, 119.86, 43.55, 29.53, 25.62, 19.44. HR-MS (ESI) m / z calcd for: C 19 H 20 NO3 + [M+H] + 310.1438, found 310.1440.

[0081] (10) 3-methyl-2-picolinoylphenyl 4-methylbenzoate (3aj): yield 68%

[0082]

[0083] 1 H NMR (600 MHz, CDC13) δ = 8.63 - 8.59 (m, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.75 - 7.70 (m, 1H), 7.56 (dd, J = 8.1, 2.7 Hz, 2H), 7.45 - 7.40 (m, 1H), 7.33 - 7.29 (m, 1H), 7.23 - 7.19 (m, 2H), 7.08 (d, J = 7.9 Hz, 2H), 2.35 (s, 3H), 2.32 (s, 3H). 13 CNMR (150 MHz, CDC13) δ = 196.43, 164.02, 154.12, 149.68, 148.36, 144.20, 137.93, 136.81, 131.83, 130.29, 129.79, 128.93, 127.94, 126.86, 126.11, 122.93, 120.10, 21.66, 19.55. HR-MS (ESI) m / z calcd for: C 21 H17NO3Na + [M+Na] + 354.1100, found 354.1098.

[0084] (11) 3-methyl-2-picolinoylphenyl 4-(tert-butyl)benzoate (3ak): yield 62%

[0085]

[0086] 1 H NMR (600 MHz, CDC13) δ = 8.62 (d, J = 4.4 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.76 - 7.71 (m, 1H), 7.64 - 7.60 (m, 2H), 7.45 - 7.40 (m, 1H), 7.33 - 7.29 (m, 3H), 7.23 - 7.19 (m, 2H), 2.31 (s, 3H), 1.29 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 196.43, 164.03, 157.17, 154.14, 149.72, 148.39, 137.86, 136.78, 131.89, 130.26, 129.70, 127.89, 126.83, 126.12, 125.19, 123.00, 120.12, 35.08, 31.04, 19.56. HR-MS (ESI) m / z calcd for: C 24 H 23 NO3Na + [M+Na] + 396.1570, found 396.1572.

[0087] (12) 3-methyl-2-picolinoylphenyl benzoate (3al): yield 58%

[0088]

[0089] 1 H NMR (600 MHz, CDC13) δ = 8.63 - 8.60 (m, 1H), 8.02 - 7.99 (m, 1H), 7.73 - 7.70 (m, 1H), 7.68 (dd, J = 8.3, 1.4 Hz, 2H), 7.50 - 7.46 (m, 1H), 7.45 - 7.43 (m, 1H), 7.31 - 7.27 (m, 3H), 7.24 - 7.21 (m, 2H), 2.33 (s, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.35, 163.98, 154.11, 149.69, 148.34, 138.02, 136.84, 133.37, 131.82, 130.33, 129.75, 128.90, 128.22, 128.06, 126.88, 122.95, 120.08, 19.56. HR-MS (ESI) m / z calcd for: C 20H 16 NO3 + [M+H] + 318.1125, found 318.1126.

[0090] (13) 3-methyl-2-picolinoylphenyl 2,4,6-trimethylbenzoate (3am): yield 63%

[0091]

[0092] 1 H NMR (600 MHz, CDC13) δ = 8.68 - 8.67 (m, 1H), 8.06 (d, J = 7.7 Hz, 1H), 7.83 - 7.79 (m, 1H), 7.44 - 7.40 (m, 2H), 7.23 (d, J = 8.2 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 6.76 (s, 2H), 2.23 (s, 3H), 2.20 (s, 3H), 2.18 (s, 6H). 13 C NMR (150 MHz, CDC13) δ = 196.51, 167.83, 153.63, 149.89, 147.82, 139.84, 137.11, 136.90, 135.88, 132.72, 129.99, 129.34, 128.50, 127.67, 127.18, 123.24, 119.74, 21.10, 19.81, 19.51. HR-MS (ESI) m / z calcd for: C 23 H 22 NO3 + [M+H] + 360.1594, found 360.1595.

[0093] (14) 3-methyl-2-picolinoylphenyl 2-naphthoate (3an): yield 52%

[0094]

[0095] 1H NMR (600 MHz, CDC13) δ = 8.63 (d, J = 4.7 Hz, 1H), 8.18 (s, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.80 (dd, J = 22.1, 8.2 Hz, 2H), 7.75 - 7.70 (m, 2H), 7.68 - 7.63 (m, 1H), 7.59 - 7.55 (m, 1H), 7.53 - 7.49 (m, 1H), 7.48 - 7.44 (m, 1H), 7.30 - 7.26 (m, 2H), 7.24 (d, J = 7.6 Hz, 1H), 2.35 (s, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.44, 164.13, 154.19, 149.70, 148.41, 138.10, 136.85, 135.61, 132.15, 131.82, 131.46, 130.39, 129.34, 128.55, 128.12, 128.05, 127.72, 126.88, 126.70, 126.09, 125.04, 122.92, 120.10, 19.59. HR-MS (ESI) m / z calcd for: C 24 H 18 NO3 + [M+H] + 368.1281, found 368.1283.

[0096] (15) 3-methyl-2-picolinoylphenyl thiophene-2-carboxylate (3ao): yield 56%

[0097]

[0098] 1 H NMR (600 MHz, CDC13) δ = 8.65 - 8.58 (m, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.79 - 7.73 (m, 1H), 7.53 - 7.50 (m, 1H), 7.49 - 7.45 (m, 1H), 7.45 - 7.40 (m, 1H), 7.35 - 7.31 (m, 1H), 7.23 (dd, J = 18.1, 8.0 Hz, 2H), 6.99 - 6.95 (m, 1H), 2.32 (s, 3H). 13C NMR (150 MHz, CDC13) δ = 196.26, 159.36, 154.02, 149.71, 147.94, 138.04, 136.82, 134.33, 133.35, 132.21, 131.69, 130.28, 128.16, 127.66, 126.91, 122.97, 119.96, 19.55. HR-MS (ESI) m / z calcd for: C 18 H 13 NO3SNa + [M+Na] + 345.0508, found 346.0507.

[0099] (16) 3-methyl-2-picolinoylphenyl cinnamate (3ap): yield 53%

[0100]

[0101] 1 H NMR (600 MHz, CDC13) δ = 8.68 (d, J = 4.7 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.83 - 7.79 (m, 1H), 7.43 - 7.39 (m, 3H), 7.38 - 7.35 (m, 5H), 7.18 (dd, J = 13.1, 8.0 Hz, 2H), 6.15 (d, J = 15.9 Hz, 1H), 2.30 (s, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.41, 164.19, 154.17, 149.80, 148.17, 146.21, 137.84, 136.94, 133.91, 131.81, 130.66, 130.29, 128.90, 128.17, 127.95, 126.99, 122.97, 120.03, 116.51, 19.56, 1.02. HR-MS (ESI) m / z calcd for: C 22 H 18 NO3 + [M+H] + 344.1281, found 344.1282.

[0102] (17) 3-methyl-2-picolinoylphenyl 2-(4-isobutylphenyl)propanoate (3aq): yield 80%

[0103]

[0104] 1 H NMR (600 MHz, CDC13) δ = 8.66 - 8.59 (m, 1H), 7.93 (d, J = 7.7 Hz, 1H), 7.84 - 7.78 (m, 1H), 7.44 - 7.39 (m, 1H), 7.36 - 7.30 (m, 1H), 7.12 (d, J = 7.6 Hz, 1H), 7.01 - 6.97 (m, 5H), 3.45 - 3.40 (m, 1H), 2.42 (d, J = 5.6 Hz, 2H), 2.21 (s, 3H), 1.85 - 1.79 (m, 1H), 1.25 (d, J = 6.2 Hz, 3H), 0.89 (d, J = 4.8 Hz, 6H). 13 C NMR (150 MHz, CDC13) δ = 196.23, 172.06, 153.71, 149.69, 147.97, 140.52, 137.31, 136.80, 136.58, 131.88, 129.94, 129.29, 127.67, 127.10, 126.98, 122.97, 119.61, 45.03, 44.95, 30.17, 22.40, 19.37, 18.20. HR-MS (ESI) m / z calcd for: C 26 H 28 NO3 + [M+H] + 402.2064, found 402.2066.

[0105] (18) 3-methyl-2-picolinoylphenyl 2-(4-benzoylphenyl)propanoate (3ar): yield 70%

[0106]

[0107] 1 H NMR (600 MHz, CDC13) δ = 8.59 - 8.55 (m, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.80 - 7.76 (m, 3H), 7.66 - 7.63 (m, 1H), 7.62 - 7.58 (m, 1H), 7.51 - 7.47 (m, 3H), 7.39 - 7.33 (m, 4H), 7.13 (d, J = 7.7 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 3.55 (q, J = 7.2 Hz, 1H), 2.19 (s, 3H), 1.33 (d, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDC13) δ = 196.29, 196.12, 171.45, 153.54, 149.70, 147.77, 139.65, 137.81, 137.42, 137.38, 136.93, 132.55, 131.90, 131.46, 130.06, 129.97, 129.25, 129.06, 128.62, 128.37, 127.85, 127.12, 122.88, 119.52, 45.20, 19.37, 18.15. HR-MS (ESI) m / z calcd for: C 29 H 24 NO4 + [M+H] + 450.1700, found 450.1702.

[0108] (19) 3-methyl-2-picolinoylphenyl 2-(6-methoxynaphthalen-2-yl)propanoate (3as): yield 60%

[0109]

[0110] 1 H NMR (600 MHz, CDC13) δ = 8.45 (d, J = 4.3 Hz, 1H), 7.62 - 7.56 (m, 3H), 7.45 - 7.41 (m, 1H), 7.39 (s, 1H), 7.34 - 7.30 (m, 1H), 7.21 (dd, J = 8.4, 1.9 Hz, 1H), 7.16 - 7.12 (m, 2H), 7.12 - 7.08 (m, 2H), 7.02 (d, J = 8.3 Hz, 1H), 3.93 (s, 3H), 3.64 (q, J = 7.1 Hz, 1H), 2.16 (s, 3H), 1.39 (d, J = 7.1 Hz, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.21, 171.99, 157.70, 153.28, 149.43, 147.82, 137.22, 136.39, 134.49, 133.73, 132.05, 129.86, 129.37, 128.86, 127.70, 127.14, 126.70, 126.04, 122.65, 119.60, 118.87, 105.54, 55.35, 45.28, 19.27, 18.21. HR-MS (ESI) m / z calcd for: C 27 H 24NO4 + [M+H] + 426.1700, found 426.1700.

[0111] (20) 3-methyl-2-picolinoylphenyl 2-(4-chlorophenyl)-3-methylbutanoate (3at): yield 82%

[0112]

[0113] 1 H NMR (600 MHz, CDC13) δ = 8.49 (ddd, J = 4.7, 1.8, 0.9 Hz, 1H), 7.84 - 7.80 (m, 1H), 7.75 - 7.72 (m, 1H), 7.35 - 7.30 (m, 2H), 7.13 - 7.09 (m, 3H), 7.01 - 6.98 (m, 3H), 2.99 (d, J = 10.6 Hz, 1H), 2.16 (s, 3H), 0.95 (d, J = 6.5 Hz, 3H), 0.59 (d, J = 6.7 Hz, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.24, 171.04, 153.15, 149.63, 147.54, 137.11, 136.62, 135.71, 133.03, 132.24, 129.80, 129.70, 128.59, 127.72, 127.02, 122.85, 119.49, 59.03, 31.83, 21.20, 19.92, 19.25. HR-MS (ESI) m / z calcd for: C 24 H 22 ClNO3Na + [M+Na] + 430.1180, found 430.1181.

[0114] (21) 3-methyl-2-picolinoylphenyl 2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanoate (3au): yield 81%

[0115]

[0116] 1H NMR (600 MHz, CDC13) δ = 8.65 (d, J = 4.7 Hz, 1H), 8.04 (d, J = 7.6 Hz, 1H), 7.85 - 7.81 (m, 1H), 7.43 (ddd, J = 7.6, 4.7, 1.3 Hz, 1H), 7.38 - 7.33 (m, 1H), 7.16 (d, J = 7.7 Hz, 1H), 7.09 (d, J = 8.6 Hz, 2H), 6.97 (d, J = 8.2 Hz, 1H), 6.82 - 6.77 (m, 2H), 2.86 - 2.81 (m, 1H), 2.21 (s, 3H), 1.95 (dd, J = 10.7, 7.4 Hz, 1H), 1.79 (dd, J = 7.9 Hz, 1H), 1.33 (d, J = 2.2 Hz, 6H). 13 CNMR (150 MHz, CDC13) δ = 196.11, 171.69, 154.65, 153.57, 149.85, 147.66, 137.44, 136.97, 132.03, 130.08, 129.60, 128.53, 127.99, 127.27, 123.14, 119.34, 119.19, 79.16, 60.88, 34.83, 25.84, 24.95, 19.47. HR-MS (ESI) m / z calcd for: C 26 H 23 Cl2NO4Na + [M+Na] + 506.0896, found 506.0899.

[0117] (22) 3-methyl-2-picolinoylphenyl 5-(2,5-dimethylphenoxy)pentanoate (3av): yield 83%

[0118]

[0119] 1H NMR (600 MHz, CDC13) δ = 8.70 - 8.67 (m, 1H), 8.10 - 8.07 (m, 1H), 7.82 - 7.78 (m, 1H), 7.40 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.38 - 7.34 (m, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.03 (d, J = 8.2 Hz, 1H), 7.00 (d, J = 7.4 Hz, 1H), 6.66 (d, J = 7.5 Hz, 1H), 6.59 - 6.56 (m, 1H), 3.80 (t, J = 6.2 Hz, 2H), 2.31 (s, 3H), 2.22 (s, 3H), 2.14 (s, 3H), 0.97 (s, 6H). 13 C NMR (150 MHz, CDC13) δ = 196.36, 175.22, 156.89, 153.65, 149.89, 148.11, 137.21, 136.96, 136.46, 132.06, 130.31, 129.95, 127.53, 127.22, 123.56, 123.23, 120.71, 119.61, 111.90, 67.73, 42.23, 36.64, 24.56, 21.41, 19.38, 15.78. HR-MS (ESI) m / z calcd for: C 28 H 33 NO4 + [M+H] + 446.2326, found 446.2328.

[0120] (23) 3-methyl-2-picolinoylphenyl (4S)-4-((8S,9R,10R,13S,14R,17S)-10,13-dimethyl- 3,7,12-trioxohexadecahydro-lH-cyclopenta[a]phenanthren-17-yl)pentanoate (3aw): yield 68%

[0121]

[0122] 1H NMR (600 MHz, CDC13) δ = 8.70 - 8.67 (m, 1H), 8.10 - 8.06 (m, 1H), 7.92 - 7.89 (m, 1H), 7.48 (ddd, J = 7.6, 4.7, 1.3 Hz, 1H), 7.39 - 7.36 (m, 1H), 7.15 (d, J = 7.7 Hz, 1H), 7.06 (d, J = 8.5 Hz, 1H), 2.96 - 2.76 (m, 4H), 2.37 - 2.31 (m, 3H), 2.30 - 2.26 (m, 2H), 2.24 (s, 3H), 2.22 - 2.20 (m, 1H), 2.16 - 2.11 (m, 3H), 2.06 - 2.01 (m, 3H), 1.98 - 1.95 (m, 1H), 1.92 - 1.86 (m, 2H), 1.83 - 1.79 (m, 1H), 1.65 - 1.60 (m, 2H), 1.40 (s, 3H), 1.15 - 1.10 (m, 1H), 1.05 (s, 3H), 0.90 - 0.86 (m, 1H), 0.70 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDC13) δ = 164.4, 150.1, 148.2, 140.1, 137.4, 132.0, 131.0, 129.1, 126.5, 126.1, 125.9, 122.2, 38.1, 37.7, 33.9, 31.0, 24.6, 23.0. HR-MS (ESI) m / z calcd for: C 37 H 44 NO6 + [M+H] + 598.3163, found 598.3167.

[0123] (24) 3-methyl-2-picolinoylphenyl (1R,4aR,4bR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene-1-carboxylate (3ax): yield 59%

[0124]

[0125] 1H NMR (600 MHz, CDC13) δ = 8.67 - 8.65 (m, 1H), 8.06 (d, J = 7.9 Hz, 1H), 7.82 - 7.79 (m, 1H), 7.42 (ddd, J = 7.5, 4.7, 1.2 Hz, 1H), 7.35 - 7.31 (m, 1H), 7.11 (d, J = 7.8 Hz, 1H), 6.99 (d, J = 8.2 Hz, 1H), 5.75 (s, 1H), 5.28 - 5.24 (m, 1H), 2.21 (s, 3H), 2.12 - 1.95 (m, 3H), 1.92 - 1.87 (m, 1H), 1.74 - 1.68 (m, 3H), 1.66 - 1.56 (m, 3H), 1.49 - 1.40 (m, 3H), 1.31 - 1.29 (m, 1H), 1.15 - 1.11 (m, 1H), 1.04 (s, 3H), 1.03 - 1.01 (m, 6H), 0.71 (s, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.51, 175.88, 153.54, 149.83, 148.23, 145.11, 137.10, 136.85, 135.23, 132.06, 129.84, 127.37, 127.10, 123.32, 122.53, 120.60, 119.52, 50.80, 46.72, 44.60, 38.08, 36.44, 34.91, 34.37, 27.46, 25.45, 22.36, 21.48, 20.91, 19.31, 17.88, 16.81, 13.95. HR-MS (ESI) m / z calcd for: C 33 H 40 NO3 + [M+H] + 498.3003, found 498.3005.

[0126] (25) 3-methyl-2-picolinoylphenyl oleate (3ay): yield 63%

[0127]

[0128] 1H NMR (600 MHz, CDC13) δ = 8.68 (d, J = 4.7 Hz, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.90 - 7.86 (m, 1H), 7.46 (ddd, J = 7.6, 4.7, 1.3 Hz, 1H), 7.40 - 7.35 (m, 1H), 7.15 (d, J = 7.7 Hz, 1H), 7.07 (d, J = 8.2 Hz, 1H), 5.39 - 5.31 (m, 2H), 2.24 (s, 3H), 2.06 - 1.97 (m, 6H), 1.37 - 1.26 (m, 18H), 1.19 - 1.13 (m, 4H), 0.88 (t, J = 6.9 Hz, 3H). 13 C NMR (150 MHz, CDC13) δ = 196.43, 171.22, 154.15, 149.91, 148.14, 137.62, 137.03, 131.92, 130.18, 130.12, 129.79, 127.82, 127.10, 123.07, 120.03, 33.99, 31.98, 29.85, 29.78, 29.76, 29.73, 29.60, 29.40, 29.15, 29.11, 28.98, 27.31, 27.24, 24.51, 22.76, 19.56, 14.19. HR-MS (ESI) m / z calcd for: C 31 H 42 NO3+[M+H] + 478.3316, found 478.3316.

[0129] (26) 3-methyl-2-picolinoylphenyl 2-propylpentanoate (3az): yield 70%

[0130]

[0131] 1 H NMR (600 MHz, CDC13) δ = 8.64 - 8.61 (m, 1H), 8.04 - 8.02 (m, 1H), 7.82 - 7.78 (m, 1H), 7.39 (ddd, J = 7.6, 4.7, 1.3 Hz, 1H), 7.30 - 7.26 (m, 1H), 7.06 (d, J = 7.7 Hz, 1H), 7.00 (d, J = 8.2 Hz, 1H), 2.16 - 2.12 (m, 4H), 1.32 - 1.26 (m, 2H), 1.19 - 1.14 (m, 2H), 1.09 - 1.03 (m, 4H), 0.70 (t, J = 7.3 Hz, 6H).13 C NMR (150 MHz, CDC13) δ = 196.56, 173.87, 153.85, 150.00, 147.99, 137.16, 136.95, 132.25, 129.92, 127.49, 127.19, 123.22, 119.73, 45.22, 34.05, 20.44, 19.44, 14.02. HR-MS (ESI) m / z calcd for: C 21 H 26 NO + [M+H] + 340.1907, found 340.1907.

[0132] (27) 2-picolinoyl-[l,l'-biphenyl]-3-yl pivalate (3ba): yield 71%

[0133]

[0134] 1 H NMR (600 MHz, CDC13) δ = 8.58 (ddd, J = 4.7, 1.7, 0.9 Hz, 1H), 7.91 - 7.86 (m, 1H), 7.75 - 7.69 (m, 1H), 7.55 - 7.51 (m, 1H), 7.34 - 7.30 (m, 2H), 7.24 - 7.21 (m, 3H), 7.18 - 7.15 (m, 3H), 1.03 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 195.78, 176.00, 154.14, 149.44, 148.44, 142.48, 139.67, 136.60, 131.71, 130.14, 128.98, 128.14, 127.39, 127.09, 126.68, 122.97, 121.35, 38.91, 26.71. HR-MS (ESI) m / z calcd for: C 23 H 22 NO3 + [M+H] + 360.1594, found 360.1595.

[0135] (28) 3-chloro-2-picolinoylphenyl pivalate (3ca): yield 73%

[0136]

[0137] 1 H NMR (600 MHz, CDC13) δ = 8.69 (d, J = 3.8 Hz, 1H), 8.18 - 8.14 (m, 1H), 7.92 - 7.87 (m, 1H), 7.49 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.43 - 7.39 (m, 1H), 7.32 (dd, J = 8.1, 1.0 Hz, 1H), 7.18 (dd, J = 8.2, 1.0 Hz, 1H), 1.01 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 192.82, 175.51, 152.95, 149.83, 148.93, 137.01, 131.97, 131.67, 130.46, 127.47, 126.67, 123.15, 121.08, 38.95, 26.64. HR-MS (ESI) m / z calcd for: C 17 H 17 ClNO3 + [M+H] + 318.0892, found 318.0893.

[0138] (29) 1-picolinoylnaphthalen-2-yl pivalate (3da): yield 79%

[0139]

[0140] 1 H NMR (600 MHz, CDC13) δ = 8.68 - 8.64 (m, 1H), 8.18 - 8.13 (m, 1H), 7.97 (d, J = 8.9 Hz, 1H), 7.91 - 7.87 (m, 2H), 7.70 (d, J = 8.0 Hz, 1H), 7.50 - 7.44 (m, 3H), 7.32 (d, J = 8.9 Hz, 1H), 0.98 (s, 9H). 1 3C NMR (150 MHz, CDC13) δ = 195.86, 175.94, 154.12, 149.93, 146.41, 137.02, 131.54, 131.44, 131.03, 128.34, 127.39, 127.37, 127.27, 125.89, 124.91, 123.56, 121.20, 38.91, 26.62. HR-MS (ESI) m / z calcd for: C 21 H 20 NO3 + [M+H] +334.1438, found 334.1438.

[0141] (30) 4-(tert-butyl)-2-picolinoylphenyl pivalate (3ea): yield 62%

[0142]

[0143] 1 H NMR (600 MHz, CDC13) δ = 8.72 - 8.68 (m, 1H), 8.08 - 8.04 (m, 1H), 7.91 - 7.84 (m, 1H), 7.64 (d, J = 2.5 Hz, 1H), 7.57 (dd, J = 8.6, 2.5 Hz, 1H), 7.46 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 1.34 (s, 9H), 0.98 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 194.56, 176.15, 154.57, 149.27, 148.34, 147.00, 136.92, 130.44, 129.73, 127.65, 126.67, 123.87, 121.97, 38.86, 34.62, 31.30, 26.61. HR-MS (ESI) m / z calcd for: C 21 H 26 NO3 + [M+H] + 340.1907, found 340.1905.

[0144] (31) 5-methoxy-2-picolinoyl-l,3-phenylene bis(2,2-dimethylpropanoate) (3fa): yield 61%

[0145]

[0146] 1 H NMR (600 MHz, CDC13) δ = 8.70 - 8.67 (m, 1H), 8.03 (d, J = 7.7 Hz, 1H), 7.86 - 7.82 (m, 1H), 7.46 - 7.43 (m, 1H), 6.63 (s, 2H), 3.84 (s, 3H), 1.03 (s, 18H). 13C NMR (150 MHz, CDC13) δ = 191.09, 175.65, 161.55, 154.08, 150.53, 149.64, 136.84, 126.88, 123.38, 117.82, 106.10, 55.84, 38.97, 26.68. HR-MS (ESI) m / z calcd for: C 23 H 28 NO6 + [M+H] + 414.1911, found 414.1913.

[0147] (32) 3-methyl-2-(4-methylpicolinoyl)phenyl pivalate (3ga): yield 59%

[0148]

[0149] 1 H NMR (600 MHz, CDC13) δ = 8.54 (d, J = 4.9 Hz, 1H), 7.93 - 7.89 (m, 1H), 7.39 - 7.32 (m, 1H), 7.29 - 7.27 (m, 1H), 7.13 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 8.2 Hz, 1H), 2.44 (s, 3H), 2.23 (s, 3H), 0.96 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 196.59, 175.84, 153.65, 149.71, 148.36, 148.19, 137.28, 132.12, 129.91, 127.99, 127.54, 124.11, 119.69, 38.86, 26.68, 26.63, 21.03, 19.40. HR-MS (ESI) m / z calcd for: C 19 H 22 NO3 + [M+H] + 414.1911, found 414.1913.

[0150] (33) 2-(4-bromopicolinoyl)-3-methylphenyl pivalate (3ha): yield 70%

[0151]

[0152] 1H NMR (600 MHz, CDC13) δ = 8.49 (d, J = 5.1 Hz, 1H), 8.27 (d, J = 1.8 Hz, 1H), 7.63 (dd, J = 5.1, 1.9 Hz, 1H), 7.39 - 7.36 (m, 1H), 7.15 - 7.13 (m, 1H), 7.04 (d, J = 8.4 Hz, 1H), 2.23 (s, 3H), 0.99 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 195.14, 175.75, 154.75, 150.51, 148.31, 137.39, 133.98, 131.27, 130.31, 130.22, 127.60, 126.42, 119.67, 38.88, 26.64, 19.43. HR-MS (ESI) m / z calcd for: C 18 H 19 BrNO3 + [M+H] + 376.0543, found 376.0543.

[0153] (34) 2-(isoquinoline-1-carbonyl)-3-methylphenyl pivalate (3ia): yield 73%

[0154]

[0155] 1 H NMR (600 MHz, CDC13) δ = 9.09 - 9.04 (m, 1H), 8.55 (d, J = 5.5 Hz, 1H), 7.92 - 7.89 (m, 1H), 7.80 (d, J = 5.5 Hz, 1H), 7.77 - 7.73 (m, 2H), 7.39 - 7.34 (m, 1H), 7.16 (d, J = 7.6 Hz, 1H), 6.96 (d, J = 8.1 Hz, 1H), 2.32 (s, 3H), 0.75 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 197.50, 176.07, 153.04, 148.51, 141.70, 138.03, 137.09, 133.74, 130.52, 130.14, 129.40, 127.83, 127.10, 126.65, 126.35, 124.49, 119.67, 38.75, 26.50, 19.77. HR-MS (ESI) m / z calcd for: C 22 H 22 NO3+ [M+H] + 348.1594, found 348.1594.

[0156] (35) 3,5-dimethyl-2-picolinoylphenyl pivalate (3ka): yield 60%

[0157]

[0158] 1 H NMR (600 MHz, CDC13) δ = 8.72 - 8.67 (m, 1H), 8.09 (d, J = 7.9 Hz, 1H), 7.89 - 7.84 (m, 1H), 7.45 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 6.96 (s, 1H), 6.84 (s, 1H), 2.36 (s, 3H), 2.21 (s, 3H), 0.94 (s, 9H). 13 C NMR (150 MHz, CDC13) δ = 196.35, 175.93, 154.08, 149.80, 148.35, 140.54, 137.25, 136.90, 128.99, 128.60, 127.02, 123.19, 120.24, 38.83, 26.62, 21.38, 19.43. HR-MS (ESI) m / z calcd for: C 19 H 22 NO3 + [M+H] + 312.1594, found 312.1595.

Claims

1. A method for the ruthenium-catalyzed synthesis of acyloxylated 2-benzoylpyridine compounds, characterized in that, Includes the following steps: A mixture of 2-benzoylpyridine compounds, sodium carboxylate compounds, [RuCl2(p-cymene)]2, 40% AgSbF6, and Ag2CO3 was reacted in an organic solvent for 12-24 hours. After the reaction was complete, the mixture was extracted with water and ethyl acetate. The organic layers were combined, dried, filtered, concentrated, and purified to obtain compound I. Its general reaction formula is as follows: The reaction temperature is 100℃~150℃; Formula I is selected from the following compounds, wherein R, R 1 R 2 , m, and s are defined as follows for compounds: 。 2. The method according to claim 1, characterized in that, The organic solvent is selected from one or more of PhCF3, DMF, CH3CN or DCE.

3. The method according to claim 2, characterized in that, The organic solvent is selected from DCE.

4. The method according to claim 1, characterized in that, The molar ratio of the 2-benzoylpyridine compound to the sodium carboxylate compound is 0.1~0.5:0.2~1.

0.

5. The method according to claim 4, characterized in that, The molar ratio of the 2-benzoylpyridine compound to the sodium carboxylate compound is 0.2:0.3~0.

4.

6. The method according to claim 1, characterized in that, The molar ratio of the 2-benzoylpyridine compound to AgSbF6 is 0.1~0.5:0.04~0.

1.

7. The method according to claim 1, characterized in that, The reaction temperature is 120℃.

8. The method according to claim 1, characterized in that, The equivalent ratio of the sodium carboxylate compound to Ag2CO3 is 1~2:1~2.

9. The method according to claim 8, characterized in that, The equivalent ratio of the sodium carboxylate compound to Ag2CO3 is 1:

1.

10. The method according to claim 1, characterized in that, The molar ratio of the sodium carboxylate compound to [RuCl2(p-cymene)]2 is 0.2~1.0:0.01~0.06.

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