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【结 构 式】

【分子编号】59748

【品名】[3-(cyclopropyloxy)-4-(difluoromethoxy)phenyl]methanol

【CA登记号】

【 分 子 式 】C11H12F2O3

【 分 子 量 】230.2112864

【元素组成】C 57.39% H 5.25% F 16.51% O 20.85%

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:(VIII)

The preparation of the precursor aldehyde (IX) is illustrated in Scheme 1. Alkylation of 3-hydroxy-4-(difluoromethoxy)benzaldehyde (I) with 1-bromo-2-chloroethane (II) affords the chloroethyl ether (III). After reduction of the aldehyde function of (III) with NaBH4, the resulting alcohol (IV) is protected as the corresponding silyl ether (V) with triisopropylsilyl triflate and 2,6-lutidine. Dehydrohalogenation of the chloroethyl ether moiety of (V) with NaOH under phase-transfer conditions, followed by resilylation with triisopropylsilyl triflate, leads to the vinyl ether (VI). This is converted into the cyclopropyl derivative (VII) following the Simmons-Smith procedure in the presence of chloroiodomethane and diethylzinc. Desilylation of (VII) with tertbutylammonium fluoride yields the benzylic alcohol (VIII), which is again oxidized to aldehyde (IX) employing MnO2 in CH2Cl2.

1 Girard, M.; Frenette, R.; Hamel, P.; Guay, D.; Ducharme, Y.; Blouin, M.; Friesen, R.; Cote, B.; Martins, E.; Laliberte, S. (Merck Frosst Canada Inc.); Tri-aryl-substd.-ethane PDE4 inhibitors. EP 1272488; US 6399636; WO 0170738 .
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) 59742 4-(difluoromethoxy)-3-hydroxybenzaldehyde C8H6F2O3 详情 详情
(II) 24271 1-bromo-2-chloroethane 107-04-0 C2H4BrCl 详情 详情
(III) 59743 3-(2-chloroethoxy)-4-(difluoromethoxy)benzaldehyde C10H9ClF2O3 详情 详情
(IV) 59744 [3-(2-chloroethoxy)-4-(difluoromethoxy)phenyl]methanol C10H11ClF2O3 详情 详情
(V) 59745 3-(2-chloroethoxy)-4-(difluoromethoxy)benzyl triisopropylsilyl ether; {[3-(2-chloroethoxy)-4-(difluoromethoxy)benzyl]oxy}(triisopropyl)silane C19H31ClF2O3Si 详情 详情
(VI) 59746 {[4-(difluoromethoxy)-3-(vinyloxy)benzyl]oxy}(triisopropyl)silane; 2-(difluoromethoxy)-5-{[(triisopropylsilyl)oxy]methyl}phenyl vinyl ether C19H30F2O3Si 详情 详情
(VII) 59747 cyclopropyl 2-(difluoromethoxy)-5-{[(triisopropylsilyl)oxy]methyl}phenyl ether; {[3-(cyclopropyloxy)-4-(difluoromethoxy)benzyl]oxy}(triisopropyl)silane C20H32F2O3Si 详情 详情
(VIII) 59748 [3-(cyclopropyloxy)-4-(difluoromethoxy)phenyl]methanol C11H12F2O3 详情 详情
(IX) 59749 3-(cyclopropyloxy)-4-(difluoromethoxy)benzaldehyde C11H10F2O3 详情 详情
Extended Information