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【结 构 式】

【分子编号】65140

【品名】tert-butyl 4-[(E)-3,3-difluoro-3-(4-fluorophenyl)-1-propenyl]-1-piperidinecarboxylate

【CA登记号】

【 分 子 式 】C19H24F3NO2

【 分 子 量 】355.4003096

【元素组成】C 64.21% H 6.81% F 16.04% N 3.94% O 9%

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:(XXVII)

Addition of 4-fluorophenylmagnesium bromide (XXII) to dimethyl oxalate (XXIII) leads to methyl 4-fluorobenzoylformate (XXIV). Subsequent fluorination of (XXIV) employing diethylaminosulfur trifluoride affords the gem-difluoro ester (XXV). Reduction of ester (XXV) with NaBH4 in cold MeOH gives rise to the aldehyde hemiacetal (XXVI). Then, Wittig condensation of hemiacetal (XXVI) with the ylide generated from phosphonium salt (XXI) provides olefin (XXVII). This is partly reduced to the saturated compound (XXVIII) by treatment with in situ generated diimide, and completely reduced to (XXVIII) by catalytic hydrogenation over iridium black. Cleavage of the N-Boc protecting group of (XXVIII) to furnish piperidine (XXIX) is accomplished by means of iodotrimethylsilane in CHCl3.

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
(XXI) 65138 {[1-(tert-butoxycarbonyl)-4-piperidinyl]methyl}(triphenyl)phosphonium iodide C29H35INO2P 详情 详情
(XXII) 13643 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide 352-13-6 C6H4BrFMg 详情 详情
(XXIII) 37412 methyl 2-methoxy-2-oxoacetate;dimethyl oxalate;Methyl oxalate 553-90-2 C4H6O4 详情 详情
(XXIV) 65143 methyl 2-(4-fluorophenyl)-2-oxoacetate C9H7FO3 详情 详情
(XXV) 65141 methyl 2,2-difluoro-2-(4-fluorophenyl)acetate C9H7F3O2 详情 详情
(XXVI) 65142 2,2-difluoro-2-(4-fluorophenyl)-1-methoxy-1-ethanol C9H9F3O2 详情 详情
(XXVII) 65140 tert-butyl 4-[(E)-3,3-difluoro-3-(4-fluorophenyl)-1-propenyl]-1-piperidinecarboxylate C19H24F3NO2 详情 详情
(XXVIII) 65139 tert-butyl 4-[3,3-difluoro-3-(4-fluorophenyl)propyl]-1-piperidinecarboxylate C19H26F3NO2 详情 详情
(XXIX) 65144 4-[3,3-difluoro-3-(4-fluorophenyl)propyl]piperidine C14H18F3N 详情 详情
Extended Information