【结 构 式】 |
【分子编号】51091 【品名】(2S)-3-chloro-2-hydroxypropyl 3-nitrobenzenesulfonate 【CA登记号】 |
【 分 子 式 】C9H10ClNO6S 【 分 子 量 】295.70024 【元素组成】C 36.56% H 3.41% Cl 11.99% N 4.74% O 32.46% S 10.84% |
合成路线1
该中间体在本合成路线中的序号:(IX)In this scheme various methods are shown for the synthesis of (S)-atenolol: 1. Treatment of (R)-glycidyl 4-nitrobenzenesulfonate (I) with HCl (either concentrated or with dichloromethane) provides 3-chloropropyl derivative (II), which is then coupled with isopropylamine (III) in dichloromethane to afford 3-chloropropylisopropylamine (IV). Finally, condensation of (IV) with 2-(4-hydroxyphenyl)acetamide (V) by means of KOH in MeOH gives the desired product. Alternatively, derivative (IV) can be converted into (S)-atenolol by its condensation with 2-(4-hydroxy-phenyl)acetonitrile (VI) by means of KOH to yield compound (VII), followed by hydrolysis with HCl at 40 C. 2. Condensation of (R)-glycidyl 3-nitrobenzenesulfonate (VIII) with isopropylamine (III) followed by coupling with acetamide (V) by means of potassium tert-butylate in DMSO provides the desired product. 3. Treatment of (VIII) with HCl affords 2(S)-hydroxy-3-chloropropyl-3-nitrobenzenesulfonate (IX), which is first coupled with isopropylamine (III) to give (IV) and finally condensed with amide (V). 4. Coupling of chloro derivative (IX) with benzyl-protected isopropylamine (X) provides protected derivative (XI), which is then condensed with acetamide (V) by means of KOH in MeOH to give (XII). Finally, compound (XII) is hydrogenated over Pd/C in MeOH for removal of the benzyl group.
【1】 Westfelt, A.; Andersson, L.; Birgersson, B.; Westfelt, L.; Process for preparing homochiral amines and process for preparing intermediates for the preparation thereof, and the intermediates prepared in accordance with this process. WO 9110642 . |
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) | 45631 | (2S)oxiranylmethyl 4-nitrobenzenesulfonate | C9H9NO6S | 详情 | 详情 | |
(II) | 51089 | (2S)-3-chloro-2-hydroxypropyl 4-nitrobenzenesulfonate | C9H10ClNO6S | 详情 | 详情 | |
(III) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |
(IV) | 51090 | (2S)-1-chloro-3-(isopropylamino)-2-propanol | C6H14ClNO | 详情 | 详情 | |
(V) | 32754 | p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide | 17194-82-0 | C8H9NO2 | 详情 | 详情 |
(VI) | 32753 | 2-(4-hydroxyphenyl)acetonitrile; 4-Hydroxybenzyl cyanide | 14191-95-8 | C8H7NO | 详情 | 详情 |
(VII) | 51088 | 2-(4-[[(2S)-2-hydroxy-3-(isopropylamino)propyl]oxy]phenyl)acetonitrile | C14H20N2O2 | 详情 | 详情 | |
(VIII) | 16259 | (2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate | 115314-14-2 | C9H9NO6S | 详情 | 详情 |
(IX) | 51091 | (2S)-3-chloro-2-hydroxypropyl 3-nitrobenzenesulfonate | C9H10ClNO6S | 详情 | 详情 | |
(X) | 39750 | N-benzyl-N-isopropylamine; N-benzyl-2-propanamine | 102-97-6 | C10H15N | 详情 | 详情 |
(XI) | 51092 | (2S)-1-[benzyl(isopropyl)amino]-3-chloro-2-propanol | C13H20ClNO | 详情 | 详情 | |
(XII) | 51093 | 2-[4-([(2S)-3-[benzyl(isopropyl)amino]-2-hydroxypropyl]oxy)phenyl]acetamide | C21H28N2O3 | 详情 | 详情 |