ethyl 3-bromo-4-oxo-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】53112

【品名】ethyl 3-bromo-4-oxo-1-piperidinecarboxylate

【CA登记号】95629-02-0

【分子式】C₈H₁₂BrNO₃

【分子量】250.09222

【元素组成】C 38.42% H 4.84% Br 31.95% N 5.6% O 19.19%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

The bromination of 4-oxopiperidine-1-carboxylic acid ethyl ester (I) with Br2 in chloroform gives 3-bromo-4-oxopiperidine-1-carboxylic acid ethyl ester (II), which is treated with NaOMe in methanol to yield 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylic acid ethyl ester (III). The methylation of (III) with NaH and MeI in DMF affords 3,4,4-trimethoxypiperidine-1-carboxylic acid ethyl ester (IV), which is hydrolyzed with refluxing 1% aq. H2SO4 to provide 3-methoxy-4-oxopiperidine-1-carboxylic acid ethyl ester (V). The reductocondensation of (V) with benzylamine and H2 over Pd/C in methanol in the presence of thiophene gives cis-4-amino-3-methoxypiperidine-1-carboxylic acid ethyl ester (VI), which is condensed with 4-amino-5-chloro-2-methoxybenzoic acid (VII) by means of ethyl chloroformate and TEA in chloroform to yield the benzamide (VIII). The hydrolysis of the carbamate group of (VIII) with KOH in refluxing isopropanol affords the free piperidine derivative (IX), which is finally condensed with 3-(4-fluorophenoxy)propyl chloride (X) by means of TEA and KI in hot DMF to provide the target, cisapride.

参考文献中间体

合成目标

【1】 Van Daele, G. (Janssen Pharmaceutica NV); Novel N-(3-hydroxy-4-piperidinyl)benzamide derivs.. US 4962115 .

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)	13486	Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone	29976-53-2	C₈H₁₃NO₃	详情	详情
(II)	53112	ethyl 3-bromo-4-oxo-1-piperidinecarboxylate	95629-02-0	C₈H₁₂BrNO₃	详情	详情
(III)	49556	ethyl 3-hydroxy-4,4-dimethoxy-1-piperidinecarboxylate		C₁₀H₁₉NO₅	详情	详情
(IV)	49569	ethyl 3,4,4-trimethoxy-1-piperidinecarboxylate		C₁₁H₂₁NO₅	详情	详情
(V)	49570	ethyl 3-methoxy-4-oxo-1-piperidinecarboxylate		C₉H₁₅NO₄	详情	详情
(VI)	49574	ethyl (3S,4R)-4-amino-3-methoxy-1-piperidinecarboxylate		C₉H₁₈N₂O₃	详情	详情
(VII)	12419	4-Amino-5-chloro-2-methoxybenzoic acid	7206-70-4	C₈H₈ClNO₃	详情	详情
(VIII)	49575	ethyl (3S,4R)-4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinecarboxylate		C₁₇H₂₄ClN₃O₅	详情	详情
(IX)	49576	4-amino-5-chloro-2-methoxy-N-[(3S,4R)-3-methoxypiperidinyl]benzamide		C₁₄H₂₀ClN₃O₃	详情	详情
(X)	30524	3-chloropropyl 4-fluorophenyl ether; 1-(3-chloropropoxy)-4-fluorobenzene; 1-(4-Fluorophenoxy)-3-chloropropane	1716-42-3	C₉H₁₀ClFO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The 3-bromo-4-oxopiperidine-1-carboxylic acid ethyl ester (III), an intermediate in the synthesis of cisapride, has been obtained as follows: The bromination of 4-oxopiperidine-1-carboxylic acid ethyl ester (I) with Br2 in methanol followed by neutralization of the resulting HBr with NaOMe in the same solvent gives 3-bromo-4,4-dimethoxypiperidine-1-carboxylic acid ethyl ester (II), which is finally hydrolyzed with aq. 2N HBr or HCl to afford the target intermediate 3-bromo-4-oxopiperidine-1-carboxylic acid ethyl ester (III).

参考文献中间体

合成目标

【1】 Serra Masia, J.; Lombardero Fernandez, J.; Montserrat, Vidal, C. (Laboratorios Salvat SA); Ethyl 3-bromo-4-oxo-1-piperidinecarboxylate, process for obtaining it and novel intermediates for its preparation. ES 2053394 .

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)	13486	Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone	29976-53-2	C₈H₁₃NO₃	详情	详情
(II)	53113	ethyl 3-bromo-4,4-dimethoxy-1-piperidinecarboxylate	n/a	C₁₀H₁₈BrNO₄	详情	详情
(III)	53112	ethyl 3-bromo-4-oxo-1-piperidinecarboxylate	95629-02-0	C₈H₁₂BrNO₃	详情	详情

Extended Information