• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】67841

【品名】3-amino-1-(3-(cyclohexylmethoxy)phenyl)propan-1-ol

【CA登记号】 

【 分 子 式 】C16H25NO2

【 分 子 量 】263.38004

【元素组成】C 72.97% H 9.57% N 5.32% O 12.15%

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)

Mitsunobu reaction of 3-hydroxybenzaldehyde (XI) with cyclohexylmethanol (XII) using PPh3 and DEAD in THF or condensation of 3-hydroxybenzaldehyde (XI) with cyclohexylmethyl bromide (IX) using K2CO3 and NMP in DMF at 75 °C give ether (XIII), which by reaction with acetonitrile (II) by means of LDA in THF at –78 °C or t-BuOK in THF yields the b-hydroxynitrile (XIV). Reduction of nitrile (XIV) with LiAlH4 or BH3·Me2S in THF affords the primary amine (XV), which by N-protection with Fmoc-Cl and DIEA in CH2Cl2 provides carbamate (XVI). Oxidation of secondary alcohol (XVI) with MnO2 in CH2Cl2 leads to the ketone (XVII), which is finally submitted to enantioselective reduction using (–)-DIP-Cl (prepared in situ by treating (–)-a-pinene with chloroborane-methyl sulfide complex in hexane) and DIEA in THF, followed by deprotection of the obtained N-Fmoc protected compound with DBU in THF. Alternatively, resolution of racemic emixustat (XV) can be performed using D-mandelic acid .

1 Scott, I.L., Kuksa, V.A. Orme, M.W., Little, T., gall, A., Hong, f. (Acucela, Inc.). Alkoxy compounds for disease treatment. CN 103553945, EP 2091955, JP 2011512321, US 2009326074, US 7982071, US 2012122938, US 2012214852, US 2013197096, US 8829244, WO 2009045479.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 37210 acetonitrile 75-05-8 C2H3N 详情 详情
(IX) 31767 1-(bromomethyl)cyclohexane 2550-36-9 C7H13Br 详情 详情
(XI) 28537 3-hydroxybenzaldehyde 100-83-4 C7H6O2 详情 详情
(XII) 28360 cyclohexylmethanol 100-49-2 C7H14O 详情 详情
(XIII) 67839 3-(cyclohexylmethoxy)benzaldehyde   C14H18O2 详情 详情
(XIV) 67840 3-(3-(cyclohexylmethoxy)phenyl)-3-hydroxypropanenitrile   C16H21NO2 详情 详情
(XV) 67841 3-amino-1-(3-(cyclohexylmethoxy)phenyl)propan-1-ol   C16H25NO2 详情 详情
(XVI) 67842 (9H-fluoren-9-yl)methyl (3-(3-(cyclohexylmethoxy)phenyl)-3-hydroxypropyl)carbamate   C31H35NO4 详情 详情
(XVII) 67843 (9H-fluoren-9-yl)methyl (3-(3-(cyclohexylmethoxy)phenyl)-3-oxopropyl)carbamate   C31H33NO4 详情 详情
Extended Information