Method for preparing n-protected-4-(n-methylaminomethyl)benzaldehyde

Abstract

The present invention relates to an efficient method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde, which is a key intermediate in the preparation of compounds having various pharmacological activities. More particularly, the present invention relates to an improved preparation method for synthesizing N-protected-4-(N-methylaminomethyl)benzaldehyde with a high yield through a novel synthesis pathway using, as a starting material, terephthaloyl halide or terephthalaldehyde, etc. each having a symmetrical structure, unlike conventional synthesis methods.

Description

Method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde

[0001] The present invention relates to an efficient method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde, a key intermediate in the preparation of compounds having various pharmacological activities. More specifically, the present invention relates to an improved method for synthesizing N-protected-4-(N-methylaminomethyl)benzaldehyde in excellent yield through a novel synthetic route using terephthaloyl halide or terephthalaldehyde, which have a symmetrical structure, as a starting material, unlike existing synthetic methods.

[0002] 4-(N-methylaminomethyl)benzaldehyde is a core skeleton frequently found in various physiologically and pharmacologically active compounds. Due to the reactivity of the amino group at position 4 with the aldehyde functional group, most derivatives of 4-aminomethylbenzaldehyde on the market are commercially available in a form in which a protecting group is introduced at the nitrogen. In particular, among the 4-(N-methylaminomethyl)benzaldehydes in which various protecting groups are introduced at the nitrogen, compound (1) in which a t-Butyloxycarbonyl (Boc) group is introduced at the nitrogen is noteworthy.

[0003] [Correction pursuant to Rule 91, August 6, 2025]

[0004] Due to the wide applicability of these 4-aminomethylbenzaldehyde derivatives in the production of various compounds, various synthetic methods for these substances have been developed.

[0005]

[0006] Specifically, in the case of compound 1, the existing synthetic method was based on the asymmetric structural feature in which different substituents were introduced at the 1st and 4th positions of the benzene ring, and benzoate (2 or 3) with a substituent introduced at the 4th position was used as a starting material, and the functional group introduced at the 4th position was converted to an N-Boc-N-methylaminomethyl group, and then the ester group was converted to an aldehyde group to prepare compound 1. However, this synthetic method had the problems of requiring relatively expensive materials and a long synthetic route because it used an asymmetric starting material with different substituents introduced at the 1st and 4th positions of the benzene ring, and obtaining the desired product in very low yields. Due to the absence of such an efficient synthetic route, although compound 1 is commercially available, it is rather expensive to use as a starting material in the preparation of various compounds, which significantly limits the expansion of the industrial applicability of the compound.

[0007] Accordingly, the inventors of the present invention have discovered that synthesizing 4-(N-protected-N-methylaminomethyl)benzaldehyde, a key intermediate that can be used in various pharmaceuticals, using terephthaloyl halide or terephthalaldehyde, which have a symmetrical structure, as a starting material has excellent advantages in terms of cost efficiency and yield, and thus completed the present invention.

[0008] The purpose of the present invention is to provide an improved method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, which is economical and can achieve excellent synthetic yield and reproducibility compared to existing production methods.

[0009] In order to achieve the above purpose, in one specific example of the present invention, a method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, which is a compound of the following chemical formula (1), is provided.

[0010] (a) a step of converting a compound of chemical formula (2) into a compound of chemical formula (3) by sequentially reacting ROH and methylamine in the presence of a base, regardless of the order;

[0011] (b) a step of converting the compound of chemical formula (3) into the compound of chemical formula (4) through a reduction reaction;

[0012] (c) a step of introducing a protecting group P to the amine group of the compound of chemical formula (4) to convert it into a compound of chemical formula (5); and

[0013] (d) a step of converting the compound of chemical formula (5) into the compound of chemical formula (1) by oxidation reaction;

[0014] Provided is a method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde comprising:

[0015] Chemical formula (1)

[0016]

[0017] Chemical formula (2)

[0018]

[0019] Chemical formula (3)

[0020]

[0021] Chemical formula (4)

[0022]

[0023] Chemical formula (5)

[0024]

[0025] Here,

[0026] R is straight or branched C1-C5 alkyl, phenyl or C6-C 10 It's Aryl,

[0027] X is selected from the group consisting of I, Br, and Cl,

[0028] P is an amine protecting group selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc).

[0029] In addition, in a preferred specific embodiment of the present invention, as a method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, which is a compound of the following chemical formula (1),

[0030] A method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde is provided, comprising the step of reacting a compound of formula (6) with a compound of formula (7) to convert it into a compound of formula (1):

[0031] Chemical formula (1)

[0032]

[0033] Chemical formula (6)

[0034]

[0035] Chemical formula (7)

[0036]

[0037] Here,

[0038] P is an amine protecting group selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc).

[0039] According to the present invention, an improved method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde is provided, which is economical and can achieve excellent synthetic yield and reproducibility compared to existing production methods.

[0040] In order to achieve the above purpose, in one specific example of the present invention, a method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, which is a compound of the following chemical formula (1), is provided.

[0041] (a) a step of converting a compound of chemical formula (2) into a compound of chemical formula (3) by sequentially reacting ROH and methylamine in the presence of a base, regardless of the order;

[0042] (b) a step of converting the compound of chemical formula (3) into the compound of chemical formula (4) through a reduction reaction;

[0043] (c) a step of introducing a protecting group P to the amine group of the compound of chemical formula (4) to convert it into a compound of chemical formula (5); and

[0044] (d) a step of converting the compound of chemical formula (5) into the compound of chemical formula (1) by oxidation reaction;

[0045] Provided is a method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde comprising:

[0046] Chemical formula (1)

[0047]

[0048] Chemical formula (2)

[0049]

[0050] Chemical formula (3)

[0051]

[0052] Chemical formula (4)

[0053]

[0054] Chemical formula (5)

[0055]

[0056] Here,

[0057] R is straight or branched C1-C5 alkyl, phenyl or C6-C 10 It's Aryl,

[0058] X is selected from the group consisting of I, Br, and Cl,

[0059] P is an amine protecting group selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc).

[0060] As used herein, the term "C1-C5 alkyl" means a hydrocarbon having 1 to 5 carbon atoms, and "straight-chain or branched" means that the hydrocarbon contains normal, secondary, or tertiary carbon atoms. Specifically, examples of suitable "C1-C5 alkyl" include, but are not limited to, methyl, ethyl, 1-propyl (n-propyl), 2-propyl, 1-butyl, 2-methyl-1-propyl, and 3-pentyl. In one embodiment of the present invention, a preferred "C1-C5 alkyl" is methyl or ethyl.

[0061] The term "C6-C" used in the present invention 10 "Aryl" means a monovalent aromatic hydrocarbon having 6 to 10 carbon atoms, which may be a single ring or a condensed double ring. Also, "C6-C 10 Aryl" may be substituted with additional substituents, for example, C6-C 10 The aryl group may be optionally substituted with 1 to 5 substituents selected from halogen, C1-C6 alkyl group, C1-C6 alkyl group substituted by halogen, and C1-C6 alkoxy group.

[0062] In the compound of formula 2 having a symmetrical structure that can be used in the present invention, X can be selected from the group consisting of I, Br, and Cl, but is not limited thereto. In one specific embodiment of the present invention, preferred X is Cl.

[0063] In the compound of formula 1 that can be prepared in the present invention, P is an amine protecting group and may be selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc), but is not limited thereto. In one specific embodiment of the present invention, a preferred P is t-butyloxycarbonyl (Boc).

[0064] In one specific embodiment of the present invention, step (a) of converting the compound of formula (2) into the compound of formula (3) is achieved through a sequential substitution reaction of ROH and methylamine, and is not limited by the specific reaction order and conditions of the substances. Specifically, in one preferred specific embodiment of the present invention, step (a) may be performed by reacting the compound of formula (2) with ROH and then adding methylamine to produce the compound of formula (3), but may also be produced by reacting them in the reverse order.

[0065] In one embodiment of the present invention, step (b) of converting the compound of formula (3) into the compound of formula (4) may use a reducing agent selected from, but not limited to, LiAlH4, sodium bis(2-methoxyethoxy)aluminum hydride, L-selectride, NiB, BH3, NiB, DIBAL, etc., and any general reducing agent capable of reducing the carbonyl group of the amide group and ester group present in the compound of formula (3) may be included in the scope of the present invention. In one embodiment of the present invention, a preferred reducing agent is LiAlH4.

[0066] In one specific embodiment of the present invention, the step (d) of converting the compound of formula (5) into the compound of formula (1) by oxidation reaction may use an oxidizing agent or oxidation reaction condition selected from (COCl)2 / DMSO / CH2Cl2, Dess-Martin oxidation, PCC, MnO2, etc., but is not limited thereto, and any general oxidizing agent or oxidation reaction condition capable of oxidizing the benzyl alcohol group present in the compound of formula (5) into a benzaldehyde group may be included in the scope of the present invention. In one specific embodiment of the present invention, the preferred oxidation reaction condition is (COCl)2 / DMSO / CH2Cl2.

[0067] In a preferred specific embodiment of the present invention, a method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, which is a compound of the following chemical formula (1),

[0068] A method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde is provided, comprising the step of reacting a compound of formula (6) with a compound of formula (7) to convert it into a compound of formula (1):

[0069] Chemical formula (1)

[0070]

[0071] Chemical formula (6)

[0072]

[0073] Chemical formula (7)

[0074]

[0075] Here,

[0076] P is an amine protecting group selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc).

[0077] In a preferred embodiment of the present invention, the step of converting terephthalaldehyde, a compound of formula (6), into a compound of formula (1) by reacting it with N-protected-N-methylamine, a compound of formula (7), is a method for preparing a compound of formula (1) in a single step through a reductive amination reaction, and all reaction conditions applicable to the above reaction may be included in the scope of the present invention.

[0078] Any suitable solvent may be used in the methods of the present invention. Representative solvents include, but are not limited to, pentane, pentanes, hexane, hexanes, heptanes, heptanes, petroleum ether, cyclopentane, cyclohexane, benzene, toluene, xylene, dichloromethane, trifluoromethylbenzene, halobenzenes such as chlorobenzene, fluorobenzene, dichlorobenzene, and difluorobenzene, methylene chloride, chloroform, acetone, ethyl acetate, diethyl ether, tetrahydrofuran (THF), 2-methyltetrahydrofuran, dibutyl ether, diisopropyl ether, methyl tert-butyl ether, dimethoxyethane, dioxane (1.4 dioxane), N-methyl pyrrolidinone (NMP), DMF, alcohols such as methanol, ethanol, propanol, butanol, or mixtures thereof.

[0079] The reaction mixture of each step of the present invention may be at any suitable pressure. For example, the reaction mixture may be at atmospheric pressure. The reaction mixture may also be exposed to any suitable environment, such as atmospheric gas or an inert gas such as nitrogen or argon.

[0080] The reaction of each step of the present invention can be carried out at any suitable temperature. For example, the temperature of the mixture during the reaction can be -78°C to 100°C, or -50°C to 150°C, or -25°C to 100°C, or 0°C to 100°C, or room temperature to 100°C, or 50°C to 100°C.

[0081]

[0082] The present invention will be described in more detail with reference to the following examples. However, the following examples are intended to aid understanding of the present invention, and the scope of the present invention is not limited to the following examples.

[0083]

[0084] General procedure

[0085] Unless otherwise noted, all reactions were performed in oven-dried glassware under an argon atmosphere. Unless otherwise noted, all reactions were magnetically stirred and monitored by analytical thin layer chromatography (TLC) using silica gel glass plates (0.25 mm) pre-coated with F254 indicator and visualized with UV light (254 nm). Flash column chromatography was performed using silica gel 60 (230-400 mesh) with the indicated eluent. Commercial grade reagents were used without further purification. Unless otherwise noted, yields refer to chromatographically and spectroscopically pure compounds. 1 H NMR and 13 C NMR spectra were recorded on 500 MHz and 125 MHz spectrometers, respectively. Tetramethylsilane (δ TMS: 0.0 ppm) and residual NMR solvent (CDCl3(δ H : 7.26ppm, δ C : 77.16ppm) or (CD3)2SO (δ H : 2.50ppm, δ C : 39.52ppm) respectively 1 H NMR and 13 C NMR spectra were used as internal standards. Proton spectra were expressed as δ (proton position, multiplicity, coupling constant J, number of protons). Multiplicities were expressed as s (singlet), d (doublet), t (triplet), q (quartet), p (quintet), m (multiplet), and br (broad). High-resolution mass spectra (HRMS) were recorded on a quadrupole time-of-flight mass spectrometer (QTOF-MS) using electrospray ionization (ESI) as the ionization method.

[0086]

[0087] In a preferred embodiment of the present invention, a novel synthetic route for preparing N-Boc-4-(N-methylaminomethyl)benzaldehyde, a compound of chemical formula (1), is as follows:

[0088] [Correction pursuant to Rule 91, August 6, 2025]

[0089] Synthesis Example 1: Synthesis of 4-(N-Boc-N-methylaminomethyl)benzaldehyde (1)

[0090] Manufacturing Example 1: Synthesis of 4-methoxycarbonyl-N-methylbenzamide

[0091]

[0092] Terephthaloyl chloride (6, 10 g, 50 mmol) was dissolved in dichloromethane (500 mL), and triethylamine (7.0 mL, 50 mmol) and methanol (2.0 mL, 50 mmol) were added, followed by stirring at 0°C for 1 h. To the reaction mixture, triethylamine (28 mL, 200 mmol) and a methanol solution of methylamine (40%, 5.1 mL, 50 mmol) were added, and the mixture was stirred at 35°C. After the reaction was completed, extraction was performed using dichloromethane and water. The obtained organic layer was dried over magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained reaction mixture was purified by column chromatography using a mixed solution of dichloromethane and methanol (9:1) as an eluent to obtain compound 7 (7.2 g, 37.5 mmol, 75%).

[0093] 1 H NMR (500 MHz, CDCl3)δ8.05 (d, J = 8.4 Hz, 2H) 7.80 (d, J = 8.4 Hz, 2H) 6.52 (br, 1H) 3.92 (s, 3H) 3.00 (d, J = 4.9 Hz, 3H)

[0094]

[0095] Manufacturing Example 2: 4-(N-Boc-N-methylaminomethyl)benzyl alcohol

[0096]

[0097] Compound 7 (7.2 g, 37.5 mmol) was dissolved in tetrahydrofuran (375 mL) and cooled to 0°C. Lithium aluminum hydride (8.5 g, 225 mmol) was slowly added to the cooled reaction mixture and stirred at room temperature for 1 hour. The reaction mixture was then refluxed at high temperature. After the reaction was completed, extraction was performed using dichloromethane and a 1.0 M aqueous sodium hydroxide solution. The obtained organic layer was dried over magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained mixture was dissolved in dichloromethane (375 mL), di-tert-butyl dicarbonate (12 g, 56 mmol) was added, and the mixture was stirred at room temperature. After the reaction was completed, extraction was performed using dichloromethane and water. The obtained organic layer was dried over magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained reaction mixture was purified by column chromatography using a mixed solution of dichloromethane and methanol (9:1) as a developing solution to obtain compound 5 (7.5 g, 30 mmol, 80%) in two steps.

[0098] 1 H NMR (500 MHz, CDCl3)δ7.32 (d, J = 7.9 Hz, 2H) 7.20 (d, J = 7.8 Hz, 2H) 4.67 (s, 2H) 4.40 (s, 2H) 2.79 (br, 3H) 2.08 (br, 1H) 1.47 (s, 9H).

[0099] Manufacturing Example 3: 4-(N-Boc-N-methylaminomethyl)benzaldehyde

[0100]

[0101] Oxalyl chloride (2.8 mL, 33 mmol) was dissolved in dichloromethane (150 mL) and cooled to -78°C. Dimethyl sulfoxide (4.7 mL, 66 mmol) was slowly added to the cooled reaction mixture and stirred for 10 minutes. A dichloromethane solution (150 mL) of compound 5 (7.5 g, 30 mmol) was slowly added to the reaction mixture and stirred for 10 minutes. Triethylamine (21 mL, 150 mmol) was added to the reaction mixture and stirred for 5 minutes, then warmed to room temperature and stirred. After the reaction was completed, extraction was performed using dichloromethane and water. The obtained organic layer was dried over magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained reaction mixture was purified by column chromatography using a mixed solution of dichloromethane and methanol (9:1) as an eluent to obtain compound 1 (7.0 g, 28.2 mmol, 94%).

[0102] 1 H NMR (500 MHz, CDCl3)δ10.00 (s, 1H), 7.86 (d, J = 8.1 Hz, 2H), 7.38 (br, 2H), 4.49 (br, 2H), 2.95 - 2.77 (m, 3H), 1.54 - 1.41 (m, 9H)

[0103]

[0104] Synthesis Example 2: Synthesis of 4-(N-Boc-N-methylaminomethyl)benzaldehyde (1)

[0105]

[0106] Terephthalaldehyde (9, 6.7 g, 50 mmol) and N-Boc-N-methylamine (14 mL, 100 mmol) were dissolved in acetonitrile (50 mL) and cooled to 0°C. Chlorodimethylsilane (17 mL, 150 mmol) was added to the reaction solution and stirred at the same temperature for 6 minutes. The reaction mixture was diluted with dichloromethane, and a saturated aqueous sodium bicarbonate solution was added, followed by vigorous stirring. The reaction mixture was extracted with dichloromethane, and the obtained organic layer was dried over magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained reaction mixture was purified by column chromatography using a mixed solution of ethyl acetate, dichloromethane, and hexane (1:20:20 to 3:20:20) as a developing solution to obtain compound 1 (3.9 g, 15.6 mmol, 31%), and unreacted terephthalaldehyde (9) (2.4 g, 17.6 mmol, 35%) was recovered.

[0107] 1 H NMR (500 MHz, CDCl3)δ10.00 (s, 1H), 7.86 (d, J = 8.1 Hz, 2H), 7.38 (br, 2H), 4.49 (br, 2H), 2.95 - 2.77 (m, 3H), 1.54 - 1.41 (m, 9H)

[0108]

[0109] Although the present invention has been described with reference to exemplary embodiments as described above, it is to be understood that the present invention is not limited to the embodiments disclosed herein, and that various modifications may be made by those skilled in the art within the scope of the technical spirit of the present invention. Furthermore, even if the operational effects according to the configuration of the present invention have not been explicitly described while describing the embodiments of the present invention, it is natural that the effects predictable by the corresponding configuration should also be acknowledged.

Claims

1. A method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, a compound of the following chemical formula (1), (a) a step of converting a compound of chemical formula (2) into a compound of chemical formula (3) by sequentially reacting ROH and methylamine in the presence of a base, regardless of the order; (b) a step of converting the compound of chemical formula (3) into the compound of chemical formula (4) through a reduction reaction; (c) a step of introducing a protecting group P to the amine group of the compound of chemical formula (4) to convert it into a compound of chemical formula (5); and (d) a step of converting the compound of chemical formula (5) into the compound of chemical formula (1) by oxidation reaction; Method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde comprising: Chemical formula (1) Chemical formula (2) Chemical formula (3) Chemical formula (4) Chemical formula (5) Here, R is straight or branched C1-C5 alkyl, phenyl or C6-C 10 It's Aryl, X is selected from the group consisting of I, Br, and Cl, P is an amine protecting group selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc).

2. A method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde in the first paragraph, wherein X is Cl.

3. A method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde in claim 1 or 2, wherein P is t-butyloxycarbonyl (Boc).

4. A method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, wherein the reducing agent used in step (b) is selected from the group consisting of LiAlH4, sodium bis(2-methoxyethoxy)aluminum hydride, L-selectride, BH3, NiB, and DIBAL.

5. A method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde, a compound of the following chemical formula (1), A method for preparing N-protected-4-(N-methylaminomethyl)benzaldehyde, comprising the step of converting a compound of formula (6) into a compound of formula (1) by reacting the compound of formula (7): Chemical formula (1) Chemical formula (6) Chemical formula (7) Here, P is an amine protecting group selected from the group consisting of methoxycarbonyl, ethoxycarbonyl, diisopropylmethoxycarbonyl, t-butyloxycarbonyl (Boc), carbobenzyloxy (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), acetyl (Ac), benzoyl (Bz), benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts), 2,2,2-trichloroethoxycarbonyl (Troc), 2-trimethylsilylethoxycarbonyl (Teoc), and aryloxycarbonyl (Alloc).

6. A method for producing N-protected-4-(N-methylaminomethyl)benzaldehyde in the fifth paragraph, wherein P is t-butyloxycarbonyl (Boc).

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