methyl carbamate; carbamic acid methyl ester -Drug Synthesis Database

【结构式】

【分子编号】40724

【品名】methyl carbamate; carbamic acid methyl ester

【CA登记号】598-55-0

【分子式】C₂H₅NO₂

【分子量】75.06724

【元素组成】C 32% H 6.71% N 18.66% O 42.63%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

The reaction of intermediate 4-(3,4-dichlorophenyl)-4-phenylbutyric acid (I) (see scheme number 09017202a intermediate (VII)) with (COCl)2 in dichloromethane gives the acyl chloride (II), which is condensed with methyl carbamate (III) in hot toluene to yield N-[4-(3,4-dichlorophenyl)-4-phenylbutyryl]carbamic acid methyl ester (IV). The reduction of (IV) with DIBAL in toluene/dichloromethane affords the hydroxybutyl derivative (V), which is cyclized by means of TiCl4 in dichloromethane to provide N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthyl]carbamic acid methyl ester as a mixture of the cis and trans isomers, easily separated by chromatography. Finally, the desired cis isomer (VI) is reduced with LiAlH4 in THF to afford the target (rac)-sertraline.

参考文献中间体

合成目标

【1】 DeNinno, M.P.; et al.; The preparation and intra- and intermolecular addition reactions of acyclic N-acylimines: Applications to the synthesis of (±)-sertraline. J Org Chem 2001, 66, 21, 6988.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	30581	4-(3,4-dichlorophenyl)-4-phenylbutyric acid		C₁₆H₁₄Cl₂O₂	详情	详情
(II)	30582	4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride		C₁₆H₁₃Cl₃O	详情	详情
(III)	40724	methyl carbamate; carbamic acid methyl ester	598-55-0	C₂H₅NO₂	详情	详情
(IV)	58595	methyl 4-(3,4-dichlorophenyl)-4-phenylbutanoylcarbamate		C₁₈H₁₇Cl₂NO₃	详情	详情
(V)	58596	methyl 4-(3,4-dichlorophenyl)-1-hydroxy-4-phenylbutylcarbamate		C₁₈H₁₉Cl₂NO₃	详情	详情
(VI)	34049	methyl (1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenylcarbamate		C₁₈H₁₇Cl₂NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

Condensation of 4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid (VIII) with methyl carbamate (XV) by means of TsOH in refluxing toluene gives the substituted furanone (XVI), which is hydrogenated with H2 over Pd/C in hot ethanol to yield 4-(2,3-dimethoxyphenyl)-2-(methoxycarbonylamino)butyric acid (XVII). Cyclization of acid (XVII) by means of PPA at 60 C affords tetralone (XVIII), which is reduced with H2 over Pd/C in an autoclave at 80 C to provide N-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)carbamic acid methyl ester (XIX). Finally, the carbamoyl group of (XIX) is reduced with LiAlH4 in hot THF to yield N-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-methylamine (V).

参考文献中间体

合成目标

【1】 Castaner, J.; Mealy, N.E.; Bayes, M.; Leeson, P.A.; Nolomirole Hydrochloride. Drugs Fut 2001, 26, 11, 1046.
【2】 Servadio, V.; Ventura, P.; Amari, G.; Chiesi, P.; Del Canale, M.; De Fanti, R. (Chiesi Farmaceutici SpA); A process for the preparation of 5,6-dihydroxy-2-amino-1,2,3,4-tetrahydronaphthalene derivs.. WO 9529147 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	37381	N-(5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl)-N-methylamine; 5,6-dimethoxy-N-methyl-1,2,3,4-tetrahydro-2-naphthalenamine		C₁₃H₁₉NO₂	详情	详情
(VIII)	37376	(E)-4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid		C₁₂H₁₂O₅	详情	详情
(XV)	40724	methyl carbamate; carbamic acid methyl ester	598-55-0	C₂H₅NO₂	详情	详情
(XVI)	49436	methyl 5-(2,3-dimethoxyphenyl)-2-oxo-2,5-dihydro-3-furanylcarbamate		C₁₄H₁₅NO₆	详情	详情
(XVII)	49437	4-(2,3-dimethoxyphenyl)-2-[(methoxycarbonyl)amino]butyric acid		C₁₄H₁₉NO₆	详情	详情
(XVIII)	49438	methyl 5,6-dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenylcarbamate		C₁₄H₁₇NO₅	详情	详情
(XIX)	49439	methyl 5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenylcarbamate		C₁₄H₁₉NO₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：

Condensation of oxobutenoic acid (III) with methyl carbamate produced dihydrofuranone (X). Catalytic hydrogenation of this compound gave (ethoxycarbonylamino)butyric acid derivative (XI). Intramolecular cyclization of (XI) to the tetralone (XII) was carried out in hot polyphosphoric acid. After hydrogenolysis of the keto group of (XII), the resulting carbamate (XIII) was reduced with LiAlH4 to the methylamino derivative (VIII), which was finally demethylated.

参考文献中间体

合成目标

【1】 Servadio, V.; Ventura, P.; Amari, G.; Chiesi, P.; Del Canale, M.; De Fanti, R. (Chiesi Farmaceutici SpA); A process for the preparation of 5,6-dihydroxy-2-amino-1,2,3,4-tetrahydronaphthalene derivs.. WO 9529147 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40724	methyl carbamate; carbamic acid methyl ester	598-55-0	C₂H₅NO₂	详情	详情
(III)	37376	(E)-4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid		C₁₂H₁₂O₅	详情	详情
(VIII)	37381	N-(5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl)-N-methylamine; 5,6-dimethoxy-N-methyl-1,2,3,4-tetrahydro-2-naphthalenamine		C₁₃H₁₉NO₂	详情	详情
(X)	37382	ethyl 5-(2,3-dimethoxyphenyl)-2-oxo-2,5-dihydro-3-furanylcarbamate		C₁₅H₁₇NO₆	详情	详情
(XI)	37383	4-(2,3-dimethoxyphenyl)-2-[(ethoxycarbonyl)amino]butyric acid		C₁₅H₂₁NO₆	详情	详情
(XII)	37384	ethyl 5,6-dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenylcarbamate		C₁₅H₁₉NO₅	详情	详情
(XIII)	37385	ethyl 5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenylcarbamate		C₁₅H₂₁NO₄	详情	详情

Extended Information