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【结 构 式】 
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【分子编号】51073 【品名】2-(4-[[(2R)-3-chloro-2-hydroxypropyl]oxy]phenyl)acetamide 【CA登记号】 |
【 分 子 式 】C11H14ClNO3 【 分 子 量 】243.6898 【元素组成】C 54.22% H 5.79% Cl 14.55% N 5.75% O 19.7% |
合成路线1
该中间体在本合成路线中的序号：(IV)Condensation of acetamide (I) with (R)-epichlorohydrin (II) by means of either NaOH, LiOH or NaOH/benzyltrimethylammonium chloride (BTA-Cl) in H2O yields a mixture of epoxypropane (III) and chloropropanol derivative (IV) that can be converted into the desired product either by direct coupling with isopropylamine (V) in MeOH, or by first reaction of the mixture (III)/(IV) with NaOH to give (S)-(III) and next coupling with (V) as described above (1-3). Alternatively, derivative (S)-(III) can also be obtained by coupling of glycidyl nosylate (VI) with acetamide (I) by means of CsF in DMF.
| 【1】 Kitaori, K.; et al.; A practical synthesis of optically active atenolol from chiral epichlorohydrin. Chem Pharm Bull 1997, 45, 2, 412. |
| 【2】 Kitaori, K.; et al.; CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure beta-blockers. Tetrahedron 1999, 55, 50, 14381. |
| 【3】 Kitaori, K.; et al.; Convenient preparation of enantiopure atenolol by means of preferential crystallization. Chem Pharm Bull 1998, 46, 3, 505. |
| 【4】 Saragai, N.; Takehira, Y.; Kitaori, K. (Daiso Co., Ltd.); Process for producing optically active atenolol and intermediate thereof. EP 0435068 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (S)-(III) | 51074 | 2-[4-[(2S)oxiranylmethoxy]phenyl]acetamide | C11H13NO3 | 详情 | 详情 | |
| (I) | 32754 | p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide | 17194-82-0 | C8H9NO2 | 详情 | 详情 |
| (II) | 38067 | (2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin | 51594-55-9 | C3H5ClO | 详情 | 详情 |
| (III) | 51072 | 2-[4-[oxiranylmethoxy]phenyl]acetamide | C11H13NO3 | 详情 | 详情 | |
| (IV) | 51073 | 2-(4-[[(2R)-3-chloro-2-hydroxypropyl]oxy]phenyl)acetamide | C11H14ClNO3 | 详情 | 详情 | |
| (V) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |
| (VI) | 45631 | (2S)oxiranylmethyl 4-nitrobenzenesulfonate | C9H9NO6S | 详情 | 详情 |