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【结 构 式】 
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【分子编号】45462 【品名】Methyl 3-(chlorosulfonyl)propanoate; 3-(Chlorosulfonyl)propionic acid methylester 【CA登记号】15441-07-3 |
【 分 子 式 】C4H7ClO4S 【 分 子 量 】186.61588 【元素组成】C 25.74% H 3.78% Cl 19% O 34.29% S 17.18% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of 2-(4-methylphenyl)ethanol (I) with t-Bu-bromoacetate (II) in toluene in the presence of NaOH and tetrabutylammonium bromide (TBAB) provides ethoxyacetic acid derivative (III), which is converted into acetamide (V) by reaction with oxalyl chloride (IV) in toluene/DMF followed by treatment with NH4OH. Reduction of (V) by reaction with borane-tetrahydrofuran (BH3·THF) in THF yields ethanamine (VI), which is then coupled to chlorosulfonyl derivative (VII) in CH2Cl2 in the presence of TEA to afford compound (VIII). Reduction of the ester group of (VIII) by treatment with diisobutylaluminium hydride (DIBAL) in toluene furnishes aldehyde (IX), which is finally subjected to a reductive amination with benzothiazol derivative (X) by means of NaCNBH3 in MeOH/HOAc.
| 【1】 Bonnert, R.; et al.; The discovery of dual D2-receptor and beta2-adrenoceptor agonists for the treatment of airway diseases. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Poster PC161. |
| 【2】 Bonnert, R.V.; Brown, R.C.; Cage, P.A.; Ince, F.; Pairaudeau, G. (AstraZeneca plc); Benzothiazolone derivs.. JP 1999512422; US 5846989; WO 9710227 . |
| 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) | 45458 | 2-(4-methylphenyl)-1-ethanol | 699-02-5 | C9H12O | 详情 | 详情 |
| (II) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (III) | 45459 | 2-[(4-methylphenethyl)oxy]acetic acid | C11H14O3 | 详情 | 详情 | |
| (IV) | 29841 | Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride | 79-37-8 | C2Cl2O2 | 详情 | 详情 |
| (V) | 45460 | 2-[(4-methylphenethyl)oxy]acetamide | C11H15NO2 | 详情 | 详情 | |
| (VI) | 45461 | 2-[(4-methylphenethyl)oxy]ethylamine; 2-[(4-methylphenethyl)oxy]-1-ethanamine | C11H17NO | 详情 | 详情 | |
| (VII) | 45462 | Methyl 3-(chlorosulfonyl)propanoate; 3-(Chlorosulfonyl)propionic acid methylester | 15441-07-3 | C4H7ClO4S | 详情 | 详情 |
| (VIII) | 45463 | methyl 3-[([2-[(4-methylphenethyl)oxy]ethyl]amino)sulfonyl]propanoate | C15H23NO5S | 详情 | 详情 | |
| (IX) | 45464 | N-[2-[(4-methylphenethyl)oxy]ethyl]-3-oxo-1-propanesulfonamide | C14H21NO4S | 详情 | 详情 | |
| (X) | 25944 | 7-(2-aminoethyl)-4-hydroxy-1,3-benzothiazol-2(3H)-one | C9H10N2O2S | 详情 | 详情 |