Synthesis method of novel benzosuberone compound

Abstract

The invention discloses a synthesis method of a novel benzosuberone compound, and belongs to the field of organic synthesis. The preparation method comprises the following steps: uniformly stirring methyltriphenylphosphonium bromide in a solvent at room temperature, dropwise adding an n-hexane solution of n-butyllithium in an ice-water bath, stirring a reaction system at room temperature for 30-40 minutes after dropwise adding is completed, then adding an initial raw material phenanthrenequinone 1 in the ice-water bath, transferring the reaction system to 40 DEG C for reaction, and after the reaction is monitored to be complete by a TLC (Thin Layer Chromatography) dot plate, filtering, washing and drying to obtain the phenanthrenequinone 1. And pouring the reaction liquid into a silica gel chromatographic column, and simply filtering by using dichloromethane as an eluent to remove salt and phosphine oxide. And performing rotary evaporation to remove the organic solvent to obtain a crude product, and separating and purifying to obtain a target product 2. The method is short in reaction time and low in reaction cost, provides a practical method for obtaining the seven-membered rigid ring skeleton, and has potential value for synthesis of natural products and bioactive molecules.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing novel benzocycloheptanone compounds. Background Art

[0002] Seven-membered rings are widely present in various natural products and bioactive molecules, such as allocolchicine and metasequirin B, and are extremely challenging due to inherent ring strain. Studies have found that the synthesis of benzocycloheptanone compounds has rarely been reported.

[0003] Benzocycloheptanone compounds can be used as intermediates to further synthesize dibenzocycloheptenone derivatives. Cyclobenzaprine hydrochloride is a muscle relaxant developed by Merck in the United States, and dibenzocycloheptenone is a key intermediate in its synthesis. Summary of the Invention

[0004] In view of the above research background, the present invention provides a simple and efficient method for synthesizing novel benzocycloheptanone compounds. The method uses phenanthrenequinone as a starting material and obtains benzocycloheptanone compounds with a yield of 33-98% in a short time.

[0005] The present invention provides a method for synthesizing novel benzocycloheptanone compounds. The method comprises the following steps: uniformly stirring methyltriphenylphosphonium bromide in a solvent at room temperature, slowly adding dropwise a n-hexane solution of n-butyllithium in an ice-water bath, stirring the reaction system at room temperature for 30-40 minutes, adding a starting material, phenanthrenequinone 1, in an ice-water bath, transferring the reaction system to 40° C. for reaction, monitoring the completion of the reaction by TLC spot plate, pouring the reaction solution into a silica gel chromatographic column, and filtering the reaction solution using dichloromethane as an eluent to remove salts and phosphine oxide. The crude product is obtained by rotary evaporation to remove the organic solvent, and the target product 2 is obtained after separation and purification.

[0006] The solvent is tetrahydrofuran.

[0007] Furthermore, the molar ratio of phenanthrenequinone to methyltriphenylphosphonium bromide is 1:5; and the molar ratio of methyltriphenylphosphonium bromide to n-butyllithium is 1:1.

[0008] Furthermore, the separation and purification is carried out by silica gel column chromatography, and the eluent is a mixture of petroleum ether and ethyl acetate in a volume ratio of 20:1.

[0009] The above reaction of the present invention is carried out in a nitrogen atmosphere.

[0010] The reaction scheme of the present invention is as follows:

[0011]

[0012] Wherein, R is selected from one or more of H, C1-C6 alkyl, C1-C6 alkoxy, halogen, and aryl.

[0013] Furthermore, the starting material phenanthrenequinone 1 is selected from one of the following structures:

[0014]

[0015] The starting material of the invention, phenanthrenequinone, is simple and readily available, and benzocycloheptanone compounds are synthesized through a rearrangement reaction of a Wittig reagent, which requires a short reaction time and has low production costs during the reaction process. This reaction can produce a series of benzocycloheptanone compounds.

[0016] The target product 2 of the present invention can be used as an intermediate to further synthesize dibenzosuberenone derivatives. This carbon core structure exists in natural products of the colchicine class.

[0017] DETAILED DESCRIPTION

[0018]

[0019] Example 1:

[0020] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1a (20.8 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to afford the pure target product 2a (17.6 mg, 80%).

[0021] 1 H NMR (500MHz, CDCl3) δ7.73 (dd, J=7.8, 1.5Hz, 1H), 7.58 (td, J=7.6, 1.5Hz, 1H), 7.51–7.47 (m, 1H), 7.45–7.35(m,4H),7.30(dd,J=7.5,1.5Hz,1H),5.25–5.22(m,1H),5.16–5.14(m,1H),3.76(s,2H). 13C NMR(126MHz, CDCl3)δ203.0,142.7,141.3,139.3,137.5,137.2,132.6,130.4,129.6,129.0,128.61,128.55,127.7,127.6,117.2,55.9.HRMS(ESI)calcd for C 16 H 13 O[M+H] + 221.0961,found 221.0968.

[0022] Example 2:

[0023] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1b (23.6 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to afford the pure target product 2b (8.2 mg, 33%).

[0024] 1 H NMR (500MHz, CDCl3) δ7.56(d,J=2.0Hz,1H),7.41–7.35(m,2H),7.31(d,J=8.0Hz,1H),7.23(dd,J=8.0,1.9Hz ,1H),7.11(d,J=1.9Hz,1H),5.22–5.20(m,1H),5.14–5.12(m,1H),3.73(s,2H),2.404(s,3H),2.400(s,3H). 13 C NMR (126MHz, CDCl3) δ203.2,143.0,141.1,138.2,137.3,137.0,136.6,134.3,133 .5,130.3,129.5,129.33,129.26,128.1,116.8,55.7,21.0,20.9.HRMS(ESI)calcd for C 18 H 16 ONa[M+Na]+ 271.1094,found271.1101.

[0025] Example 3:

[0026] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1c (36.6 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to afford the pure target product 2c (18.8 mg, 50%).

[0027] 1 H NMR (600MHz, CDCl3) δ7.64–7.60(m,2H),7.59–7.55(m,2H),7.53(dd,J=8.1,2.0H z,1H),7.18(d,J=8.1Hz,1H),5.29–5.26(m,1H),5.19–5.16(m,1H),3.71(s,2H). 13 CNMR(151MHz, CDCl3)δ201.2,141.0,140.2,139.4,137.8,136.1,133.0,132.1,132.1,131.4,131.0,129.4,127.5,122.5,118.3,55.3.HRMS(ESI)calcd for C 16 H 11 Br2O[M+H] + 378.9151,found378.9162.

[0028] Example 4:

[0029] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1d (36.0 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to afford the pure target product 2d (18.2 mg, 49%).

[0030] 1 H NMR (600MHz, CDCl3) δ7.89(d,J=8.0Hz,1H),7.78(d,J=1.9Hz,1H),7.72(d,J=1.8Hz,1H),7.69–7.6 1(m,6H),7.51–7.45(m,4H),7.44–7.37(m,3H),5.35–5.30(m,1H),5.29–5.25(m,1H),3.84(s,2H). 13 C NMR (151MHz, CDCl3) δ202.4,145.4,142.3,141.7,140.4,140.3,139.7,137.7,136.1,130.0,129.2,12 8.93,128.89,128.5,128.22,128.18,127.6,127.4,127.3,127.1,126.4,117.5,55.7.HRMS(ESI)calcd for C 28 H 20 ONa[M+Na] + 395.1407, found 395.1411.

[0031] Example 5:

[0032] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1e (23.6 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to obtain the pure target product 2e (16.9 mg, 68%).

[0033] 1 H NMR (400MHz, CDCl3) δ7.39–7.36(m,1H),7.32–7.26(m,2H),7.25–7.19(m,2H),7.11–7.08(m,1H),5. 12–5.09(m,1H),5.07–5.05(m,1H),3.62–3.55(m,1H),3.54–3.48(m,1H),2.10(s,3H),2.05(s,3H). 13 C NMR (151MHz, CDCl3) δ205.2,143.5,141.5,139.8,137.7,136.9,135.0,132.9 ,129.8,128.0,127.4,124.6,123.9,115.4,57.1,19.5,19.4.HRMS(ESI)calcd for C 18 H 17 O[M+H] + 249.1274, found 249.1280.

[0034] Example 6:

[0035] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1f (27.6 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then purified by silica gel column chromatography (PE / EtOAc = 20:1) to afford the pure target product 2f (19.9 mg, 69%).

[0036] 1 H NMR (500MHz, CDCl3) δ7.63–7.57(m,1H),7.44(dd,J=8.1,1.3Hz,1H),7.40–7.36(m,2H),7.33(t,J=7.8Hz,1 H),7.20(dd,J=7.5,1.3Hz,1H),5.25–5.20(m,1H),5.18–5.14(m,1H),3.65–3.60(m,1H),3.59–3.53(m,1H). 13 C NMR(126MHz, CDCl3)δ202.4,143.2,141.5,140.9,135.3,134.8,134.0,132.5,132.4,130.1,129.49,129.47,125.7,125.0,117.3,56.7.HRMS(ESI)calcd for C 16 H 11 Cl2O[M+H] + 289.0182,found 289.0189.

[0037] Example 7:

[0038] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 ml) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Then, 1 g of phenanthrenequinone (26.8 mg, 0.10 mmol, 1.0 equiv) was added to the mixture at 0°C. After the addition, the reaction system was allowed to react at 40°C for 3 hours. TLC monitored the complete reaction of the starting material. The reaction solution was poured into a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain a crude product. The crude product was purified by silica gel column chromatography (PE / EtOAc = 20:1) to obtain 2 g (24.4 mg, 87%) of the pure target product.

[0039] 1 H NMR (600MHz, CDCl3) δ7.42–7.27(m,2H),7.15–7.04(m,2H),6.96–6.83(m,2H),5.18–5.16( m,1H),5.14–5.12(m,1H),3.80(s,3H),3.76(s,3H),3.70–3.64(m,1H),3.63–3.58(m,1H). 13 C NMR (151MHz, CDCl3) δ204.2,157.8,156.9,142.8,142.7,140.4,129.4,128.7,124. 2,121.7,119.6,119.2,116.1,114.2,110.5,57.0,56.1,55.8.HRMS(ESI)calcdfor C 18 H 16 O3Na[M+Na] + 303.0992,found 303.0993.

[0040] Example 8:

[0041] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 ml) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1h (36.6 mg, 0.10 mmol, 1.0 equiv) was added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC monitored the complete reaction of the starting material. The reaction solution was poured into a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain a crude product. The crude product was purified by silica gel column chromatography (PE / EtOAc = 20:1) to obtain the pure target product 2h (17.0 mg, 45%).

[0042] 1 H NMR (600MHz, CDCl3) δ7.88 (d, J=2.3Hz, 1H), 7.70 (dd, J=8.4, 2.2Hz, 1H), 7.58 (dd, J=8.3, 2.2Hz, 1H), 7.4 8(d,J=2.1Hz,1H),7.33(d,J=8.3Hz,1H),7.27(s,1H),5.32–5.28(m,1H),5.22–5.19(m,1H),3.74(s,2H). 13 C NMR(151MHz, CDCl3)δ200.8,142.8,140.7,138.6,137.0,135.5,135.2,132.0,131.8,130.9,130.5,122.9,122.3,118.6,55.2.HRMS(ESI)calcd for C 16 H 11 Br2O[M+H] + 378.9151, found 378.9164.

[0043] Example 9:

[0044] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1i (26.4 mg, 0.10 mmol, 1.0 equiv) was then added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured onto a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain the crude product, which was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to afford the pure target product 2i (24.6 mg, 89%).

[0045] 1 H NMR (600MHz, CDCl3) δ7.23–7.17(m,2H),7.13(d,J=7.6Hz,1H),7.02(d,J=7.5Hz,1H),5.09–5.06(m,1H),5. 05–5.02(m,1H),3.58–3.53(m,1H),3.52–3.47(m,1H),2.34(s,3H),2.29(s,3H),1.94(s,3H),1.88(s,3H). 13 C NMR (151MHz, CDCl3) δ205.4,143.8,140.3,139.2,137.8,137.4,136.53,136.48,135.8, 135.5,129.2,128.8,124.2,123.6,115.1,57.0,21.0,20.5,16.7,16.4.HRMS(ESI)calcd for C 20 H 21 O[M+H] + 277.1587,found277.1597.

[0046] Example 10:

[0047] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 mL) were added to a Schlenk reaction tube. n-Butyllithium (2.5 M in hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1j (26.4 mg, 0.10 mmol, 1.0 equiv) was added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured into a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain a crude product, which was then purified by silica gel column chromatography (PE / EtOAc = 20:1) to obtain the pure target product 2j (27.0 mg, 98%).

[0048] 1 H NMR (600MHz, CDCl3) δ7.19(s,1H),7.09(s,1H),7.02(s,1H),6.91(s,1H),5.12–5.07(m,1H),5.06–5. 03(m,1H),3.60–3.54(m,1H),3.53–3.47(m,1H),2.36(s,3H),2.35(s,3H),2.07(s,3H),2.02(s,3H). 13 C NMR (151MHz, CDCl3) δ205.7,143.8,141.5,139.8,137.5,137.4,136.9,136.8,134.2,1 33.7,132.1,130.5,125.2,124.5,115.1,57.0,21.0,20.9,19.5,19.4.HRMS(ESI)calcd for C 20 H 21 O[M+H] + 277.1587, found 277.1593.

[0049] Example 11:

[0050] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 ml) were added to a Schlenk reaction tube. n-Butyllithium (2.5 Min hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1k (30.4 mg, 0.10 mmol, 1.0 equiv) was added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured into a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain a crude product. The crude product was then chromatographed on a silica gel column (PE / EtOAc = 20:1) to obtain the pure target product 2k (25.0 mg, 79%).

[0051] 1 HNMR (500MHz, CDCl3) δ7.37(d,J=2.3Hz,1H),7.26(d,J=2.4Hz,1H),7.23(d,J=2.3Hz,1H),7.11(d,J=2.3Hz ,1H),5.15–5.13(m,1H),5.13–5.10(m,1H),3.60–3.54(m,1H),3.53–3.47(m,1H),2.08(s,3H),2.04(s,3H). 13 C NMR (126MHz, CDCl3) δ203.0,143.0,141.8,140.9,139.7,139.0,134.3,133.8,133.5 ,132.62,132.59,129.8,124.8,124.1,116.7,56.6,19.5,19.4.HRMS(ESI)calcdforC 18 H 15 Cl2O[M+H] + 317.0495,found317.0498.

[0052] Example 12:

[0053] Under nitrogen, methyltriphenylphosphonium bromide (178.5 mg, 0.50 mmol, 5.0 equiv) and tetrahydrofuran (2.0 ml) were added to a Schlenk reaction tube. n-Butyllithium (2.5 Min hexane, 0.20 mL, 0.50 mmol, 5.0 equiv) was slowly added dropwise to the mixture at 0°C and stirred at room temperature for 30 minutes. Phenanthrenequinone 1l (30.8 mg, 0.10 mmol, 1.0 equiv) was added to the mixture at 0°C. After the addition, the reaction system was incubated at 40°C for 3 hours. TLC confirmed the complete reaction of the starting material. The reaction solution was poured into a silica gel column and briefly filtered using dichloromethane as the eluent to remove salts and phosphine oxide. The solvent was removed by rotary evaporation to obtain a crude product. The crude product was purified by silica gel column chromatography (PE / EtOAc = 20:1) to obtain the pure target product 2l (29.8 mg, 93%).

[0054] 1 HNMR(500MHz, CDCl3)δ8.02–7.89(m,4H),7.69(d,J=8.4Hz,1H),7.56–7.49(m,2H),7.47–7.41(m,1H),7.25–7 .15(m,3H),7.02(d,J=8.6Hz,1H),5.26–5.24(m,1H),5.23–5.20(m,1H),3.85–3.78(m,1H),3.76–3.70(m,1H). 13 C NMR (126MHz, CDCl3) δ205.2,143.2,139.4,136.9,135.3,134.6,133.0,132.6,131.6,131.3,129.3,128.6, 128.23,128.20,127.9,127.3,127.0,126.3,126.2,125.8,125.7,123.6,116.4,57.8.HRMS(ESI)calcdforC 24 H 17 O[M+H] + 321.1274,found321.1285.

[0055] Example 13:

[0056] To a solution of compound 2a (44.0 mg, 0.20 mmol, 1.0 equiv) in tetrahydrofuran (2.0 mL) was added aqueous sodium hydroxide (1.0 M, 0.30 mL, 0.30 mmol, 1.5 equiv) at room temperature, and the mixture was stirred at room temperature for 2 hours. TLC confirmed the completion of the reaction, and the reaction mixture was poured into water and extracted with dichloromethane (10.0 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was removed by rotary evaporation to afford the crude product, which was then purified by silica gel column chromatography (PE / EtOAc = 20:1) to afford the pure desired product 3a (35.8 mg, 81%).

[0057] 1 H NMR (500MHz, CDCl3) δ7.83–7.79(m,2H),7.77–7.71(m,2H),7.66–7.61(m,1H), 7.56–7.51(m,1H),7.50–7.46(m,2H),6.65–6.60(m,1H),2.45(d,J=1.2Hz,3H). 13 C NMR (126MHz, CDCl3) δ194.0,144.8,142.0,137.5,137.3,135.6,133.2,131.9,131.2,129.9,128.6,128.1,127.8,127.3,127.1,24.4.HRMS(ESI)calcd for C 16 H 13 O[M+H] + 221.0961,found221.0973.

[0058] Example 14:

[0059] To a solution of compound 2c (37.8 mg, 0.10 mmol, 1.0 equiv) in tetrahydrofuran (2.0 mL) was added aqueous sodium hydroxide (1.0 M, 0.15 mL, 0.15 mmol, 1.5 equiv) at room temperature, and the mixture was stirred at room temperature for 2 hours. TLC confirmed the completion of the reaction, and the reaction mixture was poured into water and extracted with dichloromethane (10.0 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was removed by rotary evaporation to afford the crude product, which was then purified by silica gel column chromatography (PE / EtOAc = 20:1) to afford the pure desired product 3c (22.7 mg, 60%).

[0060] 1H NMR (600MHz, CDCl3) δ7.91(d,J=1.9Hz,1H),7.85(d,J=2.0Hz,1H),7.68(dd,J=8.4,1.8Hz,1H),7.65–7.57(m,3H),6.59(s,1H),2.42(s,3H). 13 C NMR (151MHz, CDCl3) δ192.4,144.2,140.7,137.8,137.5,134.7,134.2,133.5,132.5,131.8,131.4,129.3,128.9,126.2,122.8,24.4.HRMS(ESI)calcd for C 16 H 11 Br2O[M+H] + 378.9151,found378.9160.

[0061] Example 15:

[0062] To a solution of compound 2d (37.2 mg, 0.10 mmol, 1.0 equiv) in tetrahydrofuran (2.0 mL) was added aqueous sodium hydroxide (1.0 M, 0.15 mL, 0.15 mmol, 1.5 equiv) at room temperature and stirred for 2 hours. TLC confirmed the completion of the reaction. The reaction mixture was poured into water and extracted with dichloromethane (10.0 mL x 2). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The solvent was removed by rotary evaporation to afford the crude product, which was then purified by silica gel column chromatography (PE / EtOAc = 20:1) to afford the pure desired product 3d (29.0 mg, 78%).

[0063] 1 H NMR (600MHz, CDCl3) δ8.06(d,J=1.7Hz,1H),8.03(d,J=2.0Hz,1H),7.92(d,J=8.0Hz,1H),7.84(d,J=8.3Hz,1H),7.80(dd,J=8.1,1.7Hz, 1H),7.74(dd,J=8.3,2.0Hz,1H),7.72–7.65(m,4H),7.52–7.47(m,4H),7.45–7.38(m,2H),6.68(d,J=1.4Hz,1H),2.52(d,J=1.2Hz,3H). 13C NMR(151MHz,CDCl3)δ193.4,144.7,144.1,141.4,140.8,139.93,139.87,138.1,137.9,134.7,133.4,130.5,129.02,128.99,128.9,128.21,128.18,128.0,127.8,127.4,127.2,127.1,126.6,24.5.HRMS(ESI)calcd for C 28 H 21 O[M+H] + 373.1587,found 373.1587。

Claims

1. A method for synthesizing a novel benzocycloheptanone compound, characterized in that: Methyltriphenylphosphonium bromide is stirred uniformly in a solvent at room temperature, and then n-butyl lithium is slowly added dropwise in an ice-water bath. After the addition is completed, the reaction system is stirred at room temperature for 30-40 minutes, and then the starting material phenanthrenequinone 1 is added to the system in an ice-water bath. The reaction system is transferred to 40°C for reaction. After TLC spot plate monitoring, after the reaction is complete, the reaction solution is poured into a silica gel column and filtered briefly using dichloromethane as an eluent to remove salts and phosphine oxide. The organic solvent is removed by rotary evaporation to obtain a crude product, which is separated and purified to obtain the target product 2. The synthetic route is as follows: Wherein, R is selected from one or more of H, C1-C6 alkyl, C1-C6 alkoxy, halogen, and aryl.

2. The method according to claim 1, wherein: The starting material phenanthrenequinone 1 is selected from one of the following structures:

3. The method according to claim 1, wherein: The solvent is tetrahydrofuran.

4. The method according to claim 1, wherein: The molar ratio of phenanthrenequinone 1 and methyltriphenylphosphonium bromide is 1:

5.

5. The method according to claim 1, wherein: The molar ratio of methyltriphenylphosphonium bromide and n-butyllithium is 1:

1.

6. The method according to claim 1, wherein: The separation and purification is carried out by silica gel column chromatography, and the eluent is a mixture of petroleum ether and ethyl acetate in a volume ratio of 20:

1.

7. The method according to claim 1, wherein: The reaction was carried out under a nitrogen atmosphere.

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