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【结 构 式】 
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【分子编号】68423 【品名】4-(5-(2-bromo-1,1-dimethoxyethyl)-3-(tert-butyl)-2-methoxyphenyl)morpholine 【CA登记号】 |
【 分 子 式 】C19H30BrNO4 【 分 子 量 】416.356 【元素组成】C 54.81% H 7.26% Br 19.19% N 3.36% O 15.37% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)Bromination of 1-(3-tert-butyl-4-hydroxyphenyl)ethanone (III) with NBS in acetonitrile yields 1-(3-bromo-5-tert-butyl-4-hydroxyphenyl)ethanone (XXV), which by protection with trimethyl orthoformate (XXVI) in the presence of (±)-CSA in MeOH affords the dimethyl acetal (XXVII). O-Methylation of phenol (XXVII) with MeI by means of K2CO3 in DMF provides 1-bromo-3-tert-butyl-5-(1,1-dimethoxyethyl)-2-methoxybenzene (XXVIII), which by Buchwald–Hartwig condensation with morpholine (XXIX) in the presence of Pd(OAc)2, BINAP and t-BuONa in DME leads to the Narylmorpholine (XXX). Bromination of compound (XXX) with PhNMe3Br3 in THF/MeOH generates the α-bromoacetal (XXXI), which, without isolation, is finally hydrolyzed by quenching in aqueous Na2S2O3 to give bromo ketone (IX) .
| 【1】 Shimomura, N., Sasho, M., Kayano, A., Yoshizawa, K., Tsujii, M., Kuroda,H., Furukawa, K. (Eisai R&D Management Co., Ltd.). Processes for producing cyclic benzamidine derivative. CA 2515715, EP 1602646, US 2006058370, US 7375236, WO 2004078721. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXX） | 68422 | 4-(3-(tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxyphenyl)morpholine | C19H31NO4 | 详情 | 详情 | |
| (III) | 68400 | 1-(3-tert-butyl-4-hydroxyphenyl)ethanone | C12H16O2 | 详情 | 详情 | |
| (IX) | 68405 | 2-bromo-1-(3-(tert-butyl)-4-methoxy-5-morpholinophenyl)ethanone | C17H24BrNO3 | 详情 | 详情 | |
| (XXV) | 68419 | 1-(3-bromo-5-(tert-butyl)-4-hydroxyphenyl)ethanone | C12H15BrO2 | 详情 | 详情 | |
| (XXVI) | 27311 | trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate | 149-73-5 | C4H10O3 | 详情 | 详情 |
| (XXVII) | 68420 | 2-bromo-6-(tert-butyl)-4-(1,1-dimethoxyethyl)phenol | C14H21BrO3 | 详情 | 详情 | |
| (XXVIII) | 68421 | 1-bromo-3-(tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxybenzene;1-bromo-3-tert-butyl-5-(1,1-dimethoxyethyl)-2-methoxybenzene | C15H23BrO3 | 详情 | 详情 | |
| (XXIX) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (XXXI) | 68423 | 4-(5-(2-bromo-1,1-dimethoxyethyl)-3-(tert-butyl)-2-methoxyphenyl)morpholine | C19H30BrNO4 | 详情 | 详情 |