【结 构 式】 |
【分子编号】14602 【品名】N-[1-(hydroxymethyl)-2-oxo-2-phenylethyl]acetamide 【CA登记号】 |
【 分 子 式 】C11H13NO3 【 分 子 量 】207.22916 【元素组成】C 63.76% H 6.32% N 6.76% O 23.16% |
合成路线1
该中间体在本合成路线中的序号:(VI)2-Aminoacetophenone.HCl (IV) is prepared from acetophenone (I) via 2-bromoacetophenone (II) and the quaternary urotropine salt (III). Acetylation of (IV) with acetic anhydride in water in the presence of sodium hydrogen carbonate yields 2-acetamidoacetophenone (V), which is converted to 2-acetamido-3-hydroxypropiophenone.HCl (VI) with formaldehyde in water. After removing the acetyl group with hydrochloric acid in ethanol, 2-amino-3-hydroxypropiophenone.HCl (VII) is formed, which is reduced with hydrogen over Pd/C in methanol to rac-erythro-2-amino-1-phenyl-1,3-propanediol.HCl (VIII). Reductive condensation of the corresponding base (IX) with phenoxyacetone (X) and hydrogen over PtO2 affords a mixture of aminodiols epimeric at C-1' (XI). (XI) is finally converted to the corresponding hydrochloride salts, from which the salt of the less soluble [1R*,2S*(S*)]-stereoisomer, i.e., solpecainol is isolated by crystallization. Structure and purity of solpecainol have been confirmed by x-ray crystallography and HPLC-MS.
【1】 Central Res. Inst. Chem. Hung. Acad. Sci. Report (27.10.1983) 1983. |
【2】 Levai, L.; Fazekas, G.; Petocz, L.; Grasser, K. (Egis Pharmaceuticals Ltd.); Novel N-alkyl derivs. of 1-phenyl-2-amino-1,3-propandiol and process for preparing same. DE 2810482; GB 1560470; JP 1978112827; US 4259257 . |
【3】 Vida, L.; Szepesy, L.; Lakszner, K.; Comparison and evaluation of derivatization methods for gas chromatographic determination of various propanediols. Chromatographia 1984, 19, 304. |
【4】 Berényi, E.; Petócz, L.; Blaskó, G.; Nógrádi, M.; Solpecainol Hydrochloride. Drugs Fut 1991, 16, 6, 514. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
34873 | 1,3,5,7-tetraazatricyclo[3.3.1.1(3,7)]decane | 100-97-0 | C6H12N4 | 详情 | 详情 | |
(I) | 10317 | Acetophenone | 98-86-2 | C8H8O | 详情 | 详情 |
(II) | 10315 | 2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone | 70-11-1 | C8H7BrO | 详情 | 详情 |
(III) | 14599 | 2-(1-bromo-1lambda(5),3,5,7-tetraazatricyclo[3.3.1.1(3,7)]dec-1-yl)-1-phenyl-1-ethanone | C14H19BrN4O | 详情 | 详情 | |
(IV) | 14600 | 2-(chloroamino)-1-phenylethanone | C8H8ClNO | 详情 | 详情 | |
(V) | 14601 | N-(2-oxo-2-phenylethyl)acetamide | C10H11NO2 | 详情 | 详情 | |
(VI) | 14602 | N-[1-(hydroxymethyl)-2-oxo-2-phenylethyl]acetamide | C11H13NO3 | 详情 | 详情 | |
(VII) | 14603 | 2-(Cloroamino)-3-hydroxy-1-phenyl-1-propanone | C9H10ClNO2 | 详情 | 详情 | |
(VIII) | 14604 | (1R,2S)-2-(Chloroamino)-1-phenylpropane-1,3-diol | C9H12ClNO2 | 详情 | 详情 | |
(IX) | 14605 | (1R,2S)-2-amino-1-phenyl-1,3-propanediol | C9H13NO2 | 详情 | 详情 | |
(X) | 10875 | 1-Phenoxyacetone; 1-Phenoxy-2-propanone | 621-87-4 | C9H10O2 | 详情 | 详情 |
(XI) | 14607 | (1R,2S)-2-[(1-methyl-2-phenoxyethyl)amino]-1-phenyl-1,3-propanediol | C18H23NO3 | 详情 | 详情 |