(2S,4S)-4-phenyl-2-pyrrolidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】38572

【品名】(2S,4S)-4-phenyl-2-pyrrolidinecarboxylic acid

【CA登记号】

【分子式】C₁₁H₁₃NO₂

【分子量】191.22976

【元素组成】C 69.09% H 6.85% N 7.32% O 16.73%

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：(XIX)

The protection of the NH group of trans-4-hydroxy-L-proline (XII) with tert-butoxycarbonyl anhydride and NaOH in tert-butanol/water gives the N-protected proline (XIII), which is esterified with benzyl alcohol and triethylamine to the benzyl ester (XIV). The tosylation of (XIV) with tosyl chloride and pyridine affords the tosylate (XV), which is debenzylated with H2 over Pd/C yielding the tosylated proline (XVI). The arylation of (XVI) with phenyllithium (XVII) and CuBr in ether/THF affords 1-(tert-butoxycarbonyl)-4(S)-phenyl)-L-proline (XVIII), which is deprotected with TFA in chloroform giving 4(S)-phenyl-L-proline (XIX). Finally, this compound is reduced with H2 over PtO2 in ethanol providing the desired intermediate trans-4-cyclohexyl-L-proline (XI).

参考文献中间体

合成目标

【1】 Moniot, J.L.; Thottathil, J.K.; Littium diphenylcuprate reactions with 4-tosyloxy-L-prolines; An interesting stereochemical outcome. A synthesis of trans-4-phenyl-L-proline. Tetrahedron Lett 1986, 27, 2, 151.
【2】 Floyd, D.; Thottathil, J.K.; Brandt, S.; Moniot, J.L. (Bristol-Myers Squibb Co.); Method for making substd. prolines. DE 3434121; US 4501901 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(XI)	38567	(2S,4S)-4-cyclohexyl-2-pyrrolidinecarboxylic acid		C₁₁H₁₉NO₂	详情	详情
(XII)	14489	(2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid; L-Hydroxyproline	51-35-4	C₅H₉NO₃	详情	详情
(XIII)	16094	(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid	16094	C₁₀H₁₇NO₅	详情	详情
(XIV)	38568	2-benzyl 1-(tert-butyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate		C₁₇H₂₃NO₅	详情	详情
(XV)	38569	2-benzyl 1-(tert-butyl) (2S,4R)-4-[[(4-methylphenyl)sulfonyl]oxy]-1,2-pyrrolidinedicarboxylate		C₂₄H₂₉NO₇S	详情	详情
(XVI)	38570	(2S,4R)-1-(tert-butoxycarbonyl)-4-[[(4-methylphenyl)sulfonyl]oxy]-2-pyrrolidinecarboxylic acid		C₁₇H₂₃NO₇S	详情	详情
(XVII)	24014	Phenyllithium	591-51-5	C₆H₅Li	详情	详情
(XVIII)	38571	(2S,4S)-1-(tert-butoxycarbonyl)-4-phenyl-2-pyrrolidinecarboxylic acid		C₁₆H₂₁NO₄	详情	详情
(XIX)	38572	(2S,4S)-4-phenyl-2-pyrrolidinecarboxylic acid		C₁₁H₁₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIX)

The Grignard condensation of N-(benzyloxycarbonyl)-4-oxo-L-proline (XXIX) with phenylmagnesium bromide gives the 4-hydroxy-4-phenylproline derivative (XXX), which is dehydrated with TFA yielding the dehydroproline (XXXI). The hydrogenation of (XXXI) with Li in liquid ammonia affords the previously reported trans-4-phenyl-L-proline (XIX), which is hydrogenated to the corresponding cyclohexyl derivative (XI) with H2 over PtO2.

参考文献中间体

合成目标

【1】 Powell, J.R.; Cushman, D.W.; Krapcho, J.; Turk, C.; DeForrest, J.M.; Spitzmiller, E.R.; Karanewsky, D.S.; Duggan, M.; Rovnyak, G.; Schwartz, J.; et al.; Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines. J Med Chem 1988, 31, 6, 1148.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	38567	(2S,4S)-4-cyclohexyl-2-pyrrolidinecarboxylic acid	C₁₁H₁₉NO₂	详情	详情
(XIX)	38572	(2S,4S)-4-phenyl-2-pyrrolidinecarboxylic acid	C₁₁H₁₃NO₂	详情	详情
(XXIX)	11357	(2S)-1-[(Benzyloxy)carbonyl]-4-oxotetrahydro-1H-pyrrole-2-carboxylic acid	C₁₃H₁₃NO₅	详情	详情
(XXX)	38573	(2S,4S)-1-[(benzyloxy)carbonyl]-4-hydroxy-4-phenyl-2-pyrrolidinecarboxylic acid	C₁₉H₁₉NO₅	详情	详情
(XXXI)	38574	(2S)-1-[(benzyloxy)carbonyl]-4-phenyl-2,5-dihydro-1H-pyrrole-2-carboxylic acid	C₁₉H₁₇NO₄	详情	详情

Extended Information