【结 构 式】 |
【分子编号】48253 【品名】2,2-diethoxy-1-ethanol 【CA登记号】621-63-6 |
【 分 子 式 】C6H14O3 【 分 子 量 】134.17536 【元素组成】C 53.71% H 10.52% O 35.77% |
合成路线1
该中间体在本合成路线中的序号:(II)The reduction of 2,2-diethoxyacetic acid ethyl ester (I) with NaBH4 in dimethoxyethane gives 2,2-diethoxyethanol (II), which is condensed with ethyl 4-chloroacetoacetate (III) by means of NaH in hot THF to yield ethyl 4-(2,2-diethoxyethoxy)acetoacetate (IV). The condensation of (IV) with 2-chlorobenzaldehyde (V) by means of piperidine in refluxing toluene affords the acrylic ester (VI), which is cyclized with methyl 3-aminocrotonate (VII) in refluxing toluene to provide the dihydropyridine (VIII). The reaction of (VIII) with hydroxylamine in refluxing methanol/water gives the hydroxyimino derivative (IX), which is finally reduced to the target compound by means of H2 over Pd/C in acetic acid or with NaBH4 and NiCl2 in methanol. Alternatively, intermediate dihydropyridine (VIII) can be obtained as follows: The reaction of acetoacetate (IV) with ammonium acetate in refluxing ethanol gives ethyl 3-amino-4-(2,2-diethoxyethoxy)crotonate (X), which is cyclized with methyl 2-(2-chlorobenzylidene)acetoacetate (XI) in refluxing toluene to yield the target intermediate the dihydropyridine (VIII).
【1】 Pedersen, S.B.; Preikschat, H.F.; Karup, G.L. (GEA A/S Farmaceutisk Fabrik); Process for the preparation of acetal derivs. of 1,4-dihydropyridines. WO 9925689 . |
【2】 Karup, G.L.; Preikschat, H.F. (GEA A/S Farmaceutisk Fabrik); Process for the preparation of 1,4-dihydropyridines and cpds. used in this process. WO 9925688 . |
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) | 25674 | ethyl 2,2-diethoxyacetate | 6065-82-3 | C8H16O4 | 详情 | 详情 |
(II) | 48253 | 2,2-diethoxy-1-ethanol | 621-63-6 | C6H14O3 | 详情 | 详情 |
(III) | 23541 | ethyl 4-chloro-3-oxobutanoate;Ethyl 4-chloro-3-oxobutanoate;Ethyl 4-chloroacetoacetate | 638-07-3 | C6H9ClO3 | 详情 | 详情 |
(IV) | 48254 | ethyl 4-(2,2-diethoxyethoxy)-3-oxobutanoate | C12H22O6 | 详情 | 详情 | |
(V) | 24114 | 2-chlorobenzaldehyde | 89-98-5 | C7H5ClO | 详情 | 详情 |
(VI) | 48255 | ethyl (Z)-3-(2-chlorophenyl)-2-[2-(2,2-dimethoxyethoxy)acetyl]-2-propenoate | C17H21ClO6 | 详情 | 详情 | |
(VII) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 | |
(VIII) | 48256 | 3-ethyl 5-methyl 4-(2-chlorophenyl)-2-[(2,2-dimethoxyethoxy)methyl]-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate | C22H28ClNO7 | 详情 | 详情 | |
(IX) | 48258 | 3-ethyl 5-methyl 4-(2-chlorophenyl)-2-[[2-(hydroxyimino)ethoxy]methyl]-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate | C20H23ClN2O6 | 详情 | 详情 | |
(X) | 48257 | ethyl (E)-3-amino-4-(2,2-diethoxyethoxy)-2-butenoate | C12H23NO5 | 详情 | 详情 | |
(XI) | 44034 | methyl (Z)-2-acetyl-3-(2-chlorophenyl)-2-propenoate | C12H11ClO3 | 详情 | 详情 |