4-methoxybenzyl (2R)-2-[(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidinyl]-3-cyclopropylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】65135

【品名】4-methoxybenzyl (2R)-2-[(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidinyl]-3-cyclopropylpropanoate

【CA登记号】

【分子式】C₃₁H₄₄FNO₄Si

【分子量】541.7786032

【元素组成】C 68.73% H 8.19% F 3.51% N 2.59% O 11.81% Si 5.18%

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：(XV)

Diazotization of L-cyclopropylalanine (X) with NaNO2/H2SO4 gives rise to the chiral hydroxy acid (XI). Subsequent treatment of hydroxyacid (XI) with p-methoxybenzyl chloride (XII) in the presence of Et3N furnishes the corresponding p-methoxybenzyl ester (XIII). Hydroxy ester (XIII) is then converted to triflate (XIV), which is further condensed with pyrrolidine (IX) to yield amino ester (XV). Desilylation of (XV) with tetrabutylammonium fluoride affords alcohol (XVI). This is then subjected to Swern oxidation to provide aldehyde (XVII) (1).

参考文献中间体

合成目标

【1】 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Rosauer, K. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6265434; WO 0059503 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	63988	(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; tert-butyl(dimethyl)silyl [(3R,4S)-4-(3-fluorophenyl)pyrrolidinyl]methyl ether		C₁₇H₂₈FNOSi	详情	详情
(X)	65131	(2S)-2-amino-3-cyclopropylpropanoic acid		C₆H₁₁NO₂	详情	详情
(XI)	65132	(2S)-3-cyclopropyl-2-hydroxypropanoic acid		C₆H₁₀O₃	详情	详情
(XII)	11910	4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether	824-94-2	C₈H₉ClO	详情	详情
(XIII)	65133	4-methoxybenzyl (2S)-3-cyclopropyl-2-hydroxypropanoate		C₁₄H₁₈O₄	详情	详情
(XIV)	65134	4-methoxybenzyl (2S)-3-cyclopropyl-2-{[(trifluoromethyl)sulfonyl]oxy}propanoate		C₁₅H₁₇F₃O₆S	详情	详情
(XV)	65135	4-methoxybenzyl (2R)-2-[(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidinyl]-3-cyclopropylpropanoate		C₃₁H₄₄FNO₄Si	详情	详情
(XVI)	65136	4-methoxybenzyl (2R)-3-cyclopropyl-2-[(3S,4R)-3-(3-fluorophenyl)-4-(hydroxymethyl)pyrrolidinyl]propanoate		C₂₅H₃₀FNO₄	详情	详情
(XVII)	65137	4-methoxybenzyl (2R)-3-cyclopropyl-2-[(3S,4R)-3-(3-fluorophenyl)-4-formylpyrrolidinyl]propanoate		C₂₅H₂₈FNO₄	详情	详情

Extended Information