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【结 构 式】 
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【分子编号】64767 【品名】tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethylcarbamate 【CA登记号】 |
【 分 子 式 】C17H23NO5 【 分 子 量 】321.37336 【元素组成】C 63.54% H 7.21% N 4.36% O 24.89% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of bromoketone (I) with di-tert-butyl iminodicarboxylate (II) by means of Cs2CO3 in acetonitrile gives the adduct (III), which is monodecarboxylated by reaction with TFA in dichloromethane to yield the carbamate (IV). The asymmetric reduction of the ketonic group of (IV) by means of BH3 and a chiral oxazaborole catalyst affords the (R)-alcohol (V), which is cyclized by means of NaH in DMF to provide the chiral oxazolidinone (VI). The alkylation of (VI) with 6-(4-phenylbutoxy)hexyl bromide (VII) by means of NaH in THF gives the alkylated oxazolidinone (VIII), which is treated with Tms-OK in THF to cleave the oxazolidinone ring, yielding the aminoalcohol (IX). Finally, the acetonide ring of (IX) is cleaved by means of AcOH in methanol to provide salmeterol.
| 【1】 Coe, D.M.; Perciaccante, R.; Procopiou, P.A.; Potassium trimethylsilanolate induced cleavage of 1,3-oxazolidin-2 and 5-ones, and application to the synthesis of (R)-salmeterol. Org Biomol Chem 2003, 1, 7, 1106. |
| 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) | 52359 | 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1-ethanone | C12H13BrO3 | 详情 | 详情 | |
| (II) | 48447 | Di-tert-butyl iminodicarboxylate; Iminodicarboxylic acid di-tert-butyl ester | 51779-32-9 | C10H19NO4 | 详情 | 详情 |
| (III) | 64766 | 6-{2-[bis(tert-butoxycarbonyl)amino]acetyl}-2,2-dimethyl-4H-1,3-benzodioxine | C22H31NO7 | 详情 | 详情 | |
| (IV) | 64767 | tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethylcarbamate | C17H23NO5 | 详情 | 详情 | |
| (V) | 64768 | tert-butyl (2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethylcarbamate | C17H25NO5 | 详情 | 详情 | |
| (VI) | 64769 | (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one | C13H15NO4 | 详情 | 详情 | |
| (VII) | 31479 | 1-[4-[(6-bromohexyl)oxy]butyl]benzene; 6-bromohexyl-4-phenylbutyl ether; 6-Bromohexyloxybutylbenzene | 94749-73-2 | C16H25BrO | 详情 | 详情 |
| (VIII) | 64770 | (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-(4-phenylbutoxy)hexyl]-1,3-oxazolidin-2-one | C29H39NO5 | 详情 | 详情 | |
| (IX) | 52679 | (1R)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-{[6-(4-phenylbutoxy)hexyl]amino}-1-ethanol | C28H41NO4 | 详情 | 详情 |