ethyl (3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenylpentanoate -Drug Synthesis Database

【结构式】

【分子编号】25723

【品名】ethyl (3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenylpentanoate

【CA登记号】

【分子式】C₁₈H₂₇NO₅

【分子量】337.41612

【元素组成】C 64.07% H 8.07% N 4.15% O 23.71%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XIII)

Treatment of N-Boc-L-phenylalanine (XI) with carbonyl diimidazole, followed by condensation with the lithium enolate of ethyl acetate provided the beta-ketoester (XII). Then, reduction with NaBH4 in EtOH at -78 C furnished the anti aminoalcohol (XIII) as the major isomer. Subsequent reaction with formaldehyde in the presence of p-toluenesulfonic acid in boiling toluene produced the cis oxazolidine (XIV). Basic hydrolis of the ester group yielded carboxylic acid (XV) which, after activation as the mixed anhydride with 2,4,6-trichlorobenzoyl chloride (VI), was coupled to hydroxyester (X) to give triester (XVI). Reduction of the oxazolidine with NaBH3CN in the presence of trifluoroacetic acid afforded the N-methylated derivative (XVII). Then, hydrogenolysis of the benzyl ester in the presence of Pd/C produced acid (XVIII), which was finally cyclized using DPPA.

参考文献中间体

合成目标

【1】 Wagner, B.; et al.; Total synthesis and conformational studies of hapalosin, N-desmethylhapalosin and 8-deoxyhapalosin. Bioorg Med Chem 1999, 7, 5, 737.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	25718	2,4,6-trichlorobenzoyl chloride	4136-95-2	C₇H₂Cl₄O	详情	详情
(X)	25722	(1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl (2S,3R)-3-hydroxy-2-methyldecanoate		C₂₃H₃₆O₅	详情	详情
(XI)	12874	(2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine	13734-34-4	C₁₄H₁₉NO₄	详情	详情
(XII)	12876	ethyl (4S)-4-[(tert-butoxycarbonyl)amino]-3-oxo-5-phenylpentanoate		C₁₈H₂₅NO₅	详情	详情
(XIII)	25723	ethyl (3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenylpentanoate		C₁₈H₂₇NO₅	详情	详情
(XIV)	25724	tert-butyl (4S,5R)-4-benzyl-5-(2-ethoxy-2-oxoethyl)-1,3-oxazolidine-3-carboxylate		C₁₉H₂₇NO₅	详情	详情
(XV)	25725	2-[(4S,5R)-4-benzyl-3-(tert-butoxycarbonyl)-1,3-oxazolidin-5-yl]acetic acid		C₁₇H₂₃NO₅	详情	详情
(XVI)	25726	tert-butyl (4S,5R)-4-benzyl-5-[2-([(1S)-1-[(1S)-2-([(1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl]oxy)-1-methyl-2-oxoethyl]octyl]oxy)-2-oxoethyl]-1,3-oxazolidine-3-carboxylate		C₄₀H₅₇NO₉	详情	详情
(XVII)	25727	(1S)-1-[(benzyloxy)carbonyl]-2-methylpropyl (2S,3S)-3-[[(3R,4S)-3-hydroxy-4-(methylamino)-5-phenylpentanoyl]oxy]-2-methyldecanoate		C₃₅H₅₁NO₇	详情	详情
(XVIII)	25728	(2S)-2-[((2S,3S)-3-[[(3R,4S)-3-hydroxy-4-(methylamino)-5-phenylpentanoyl]oxy]-2-methyldecanoyl)oxy]-3-methylbutyric acid		C₂₈H₄₅NO₇	详情	详情

Extended Information