methyl (2S)-2-(2-oxo-1-pyrrolidinyl)butanoate -Drug Synthesis Database

【结构式】

【分子编号】61971

【品名】methyl (2S)-2-(2-oxo-1-pyrrolidinyl)butanoate

【CA登记号】

【分子式】C₉H₁₅NO₃

【分子量】185.22304

【元素组成】C 58.36% H 8.16% N 7.56% O 25.91%

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：(X)

The condensation of 2-pyrrolidinone (I) with 2-oxoacetic acid (II) in ethyl ether gives 2-hydroxy-2-(2-oxopyrrolidin-1-yl)acetic acid (III), which is fully methylated with methanol and conc. sulfuric acid to yield 2-methoxy-2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (IV). The reaction of (IV) with PCl3 in hot toluene affords 2-chloro-2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (V), which is condensed with triethyl phosphite (VI), also in hot toluene, to provide the dimethyl phosphonate (VII). The condensation of (VII) with acetaldehyde (VIII) in THF by means of tetramethylguanidine gives 2-(2-oxopyrrolidin-1-yl)-2-butenoic acid methyl ester (IX), which is reduced with H2 and a chiral Rhodium catalyst in THF to yield 2(S)-(2-oxopyrrolidin-1-yl)butyric acid methyl ester (X). Finally, this ester is treated with ammonia in methanol to afford the target chiral amide.

参考文献中间体

合成目标

【1】 Boaz, N.W.; Debenham, S.D.; Highly enantiomerically pure lactam-substd. propanoic acid derivs. and methods of making and using same. WO 0226705 .

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)	27397	2-Pyrrolidinone	616-45-5	C₄H₇NO	详情	详情
(II)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	61966	2-hydroxy-2-(2-oxo-1-pyrrolidinyl)acetic acid		C₆H₉NO₄	详情	详情
(IV)	61967	methyl 2-methoxy-2-(2-oxo-1-pyrrolidinyl)acetate		C₈H₁₃NO₄	详情	详情
(V)	61968	methyl 2-chloro-2-(2-oxo-1-pyrrolidinyl)acetate		C₇H₁₀ClNO₃	详情	详情
(VI)	12642	Trimethyl phosphite	121-45-9	C₃H₉O₃P	详情	详情
(VII)	61969	methyl 2-(dimethoxyphosphoryl)-2-(2-oxo-1-pyrrolidinyl)acetate		C₉H₁₆NO₆P	详情	详情
(VIII)	11974	Acetaldehyde	75-07-0	C₂H₄O	详情	详情
(IX)	61970	methyl (E)-2-(2-oxo-1-pyrrolidinyl)-2-butenoate		C₉H₁₃NO₃	详情	详情
(X)	61971	methyl (2S)-2-(2-oxo-1-pyrrolidinyl)butanoate		C₉H₁₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The reaction of 2(S)-aminobutyric acid (I) with SOCl2 gives the acyl chloride (II), which is treated with methanol to yield the methyl ester (III). The condensation of (III) with ethyl 4-bromobutyrate (IV) by means of Na2CO3 in refluxing water affords 2(S)-[3-(ethoxycarbonyl)propylamino)butyric acid methyl ester (V), which is cyclized by means of 2-pyridinol in refluxing toluene to provide 2(S)-(2-oxopyrrolidin-1-yl)butyric acid methyl ester (VI). Finally this compound is treated with ammonia in water to furnish the target Lavetiracetam.

参考文献中间体

合成目标

【1】 Cavoy, E.; Ates, C.; Surtees, J.; Burteau, A.-C.; Marmon, V. (UCB SA); Oxopyrrolidine cpds., preparation of said cpds. and their use in the manufacturing of levetiracetam and analogues. WO 0314080 .

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)	32037	(2S)-2-aminobutyric acid	1492-24-6	C₄H₉NO₂	详情	详情
(II)	61972	(2S)-2-aminobutanoyl chloride		C₄H₈ClNO	详情	详情
(III)	61973	methyl (2S)-2-aminobutanoate		C₅H₁₁NO₂	详情	详情
(IV)	61974	Ethyl 4-bromobutyrate; 4-Bromobutyric acid ethyl ester; Ethyl g-Bromobutyrate; Ethyl-(4-brombutyrat); 4-Bromo-n-butyric Acid Ethyl Ester; Ethyl 4-Bromo-n-butyrate; 4-Bromobutyric acid ethylester; Ethylbromobutyrate; 4-Bromobutyric Acid, Ethyl Ester; Ethyl-4-bromobutyrate; 4-BBE	2969-81-5	C₆H₁₁BrO₂	详情	详情
(V)	61975	methyl (2S)-2-[(4-ethoxy-4-oxobutyl)amino]butanoate		C₁₁H₂₁NO₄	详情	详情
(VI)	61971	methyl (2S)-2-(2-oxo-1-pyrrolidinyl)butanoate		C₉H₁₅NO₃	详情	详情

Extended Information