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【结 构 式】 
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【分子编号】31723 【品名】2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-fluorobenzaldehyde 【CA登记号】 |
【 分 子 式 】C14H20FNO3 【 分 子 量 】269.3161432 【元素组成】C 62.44% H 7.49% F 7.05% N 5.2% O 17.82% |
合成路线1
该中间体在本合成路线中的序号：(V)The reaction of 5-fluorosalicylaldehyde (I) with 1-chloro-3-(tert-butylamino)-2-propanol (II) by means of p-toluenesulfonic acid in refluxing benzene gives 5-chloromethyl-3-(tert-butyl)-2-(2-hydroxy-5-fluorophenyl)oxazolidine (III), which is cyclized again by treatment with NaH in hot DMF to afford 8-aza-4,9-dioxa-11-fluoro-8-(tert-butyl)-2,3-benzobicyclo[4.2.1]octan (IV). Hydrolysis of (IV) with aqueous 1N HCl at 80 C yields 1-(2-formyl-4-fluorophenoxy)-3-(tert-butylamino)-2-propanol (V), which is submitted to a Grignard reaction with propylmagnesium bromide (A) in refluxing ether to afford 1-[2-(1-hydroxybutyl)-4-fluorophenoxy]-3-(tert-butylamino)-2-propanol (VI). Finally, this compound is oxidized with chromic acid in acetone - H2SO4.
| 【1】 Demarne le Florence, H.; Compositions for treatment of cardiovascular conditions associated with overproduction of catecholamines. BE 0830766; CA 1052820; DE 2528147; FR 2276032; GB 1501632; JP 51023233; NL 7507703; US 4252825; US 4302601 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Neuman, M.; Butofilolol. Drugs Fut 1982, 7, 2, 96. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10970 | (4R)-4-[3-(Benzyloxy)-4-methoxyphenyl]-2-pyrrolidinone | C18H19NO3 | 详情 | 详情 | |
| (I) | 31719 | 5-fluoro-2-hydroxybenzaldehyde | C7H5FO2 | 详情 | 详情 | |
| (II) | 31720 | 1-(tert-butylamino)-3-chloro-2-propanol | C7H16ClNO | 详情 | 详情 | |
| (III) | 31721 | 2-[3-(tert-butyl)-5-(chloromethyl)-1,3-oxazolidin-2-yl]-4-fluorophenol | C14H19ClFNO2 | 详情 | 详情 | |
| (IV) | 31722 | 11-(tert-butyl)-4-fluoro-8,12-dioxa-11-azatricyclo[7.2.1.0(2,7)]dodeca-2,4,6-triene | C13H16FNO2 | 详情 | 详情 | |
| (V) | 31723 | 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-fluorobenzaldehyde | C14H20FNO3 | 详情 | 详情 | |
| (VI) | 31724 | 1-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-fluorophenyl]-1-butanol | C17H28FNO3 | 详情 | 详情 |