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【结 构 式】

【分子编号】55285

【品名】1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonyl chloride

【CA登记号】

【 分 子 式 】C20H21ClFNO2

【 分 子 量 】361.8433832

【元素组成】C 66.39% H 5.85% Cl 9.8% F 5.25% N 3.87% O 8.84%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XII)

The reaction of terephthalic acid (I) with trioxane and oleum at 140-150 C gives 1-oxo-1,3-dihydroisobenzofuran-5-carboxylic acid (II), which is treated with SOCl2 in refluxing toluene to yield the acyl chloride (III). The condensation of (III) with 2-hydroxy-1,1-dimethylethylamine (IV) in the same solvent affords the amide (V), which is cyclized by means of SOCl2 in dichloromethane to provide the oxazoline (VI). The Grignard condensation of (VI) with 4-fluorophenylmagnesium bromide (VII) in THF gives the benzophenone (VIII), which is submitted to a new Grignard condensation with 3-(dimethylamino)propylmagnesium bromide (IX) in the same solvent to yield the diol (X). Finally, this compound is treated with POCl3 or SOCl2 and POCl3 in hot pyridine to afford the target citalopram. Alternatively, the cleavage of the oxazoline ring of (X) with H2SO4 and then with NaOH gives the sodium carboxylate (XI), which is treated with SOCl2 in dichloromethane to yield the corresponding acyl chloride (XII). The reaction of (XII) with dry ammonia in the same solvent affords the carboxamide (XIII), which is finally dehydrated with POCl3 in refluxing acetonitrile to provide the target citalopram.

1 Greenwood, A.K.; McHattie, D.; Rechka, J.A.; Hedger, P.C.M.; Gamble, M.P. (Resolution Chemicals Ltd.); Process for the preparation of citalopram. WO 0166536 .
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) 54025 1,4-Benzenedicarboxylic acid; Benzene-1,4-dicarboxylic acid; p-Benzenedicarboxylic acid; p-Phthalic acid; Terephthalic acid 100-21-0 C8H6O4 详情 详情
(II) 37594 1-oxo-1,3-dihydro-2-benzofuran-5-carboxylic acid C9H6O4 详情 详情
(III) 37595 1-oxo-1,3-dihydro-2-benzofuran-5-carbonyl chloride C9H5ClO3 详情 详情
(IV) 21513 2-amino-2-methyl-1-propanol;Karl Fischer;2-Amino-2-methyl-propan-1-ol;2-amino-2-methyl-1-propanol 124-68-5 C4H11NO 详情 详情
(V) 37596 N-(2-hydroxy-1,1-dimethylethyl)-1-oxo-1,3-dihydro-2-benzofuran-5-carboxamide C13H15NO4 详情 详情
(VI) 37597 5-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-2-benzofuran-1(3H)-one C13H13NO3 详情 详情
(VII) 13643 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide 352-13-6 C6H4BrFMg 详情 详情
(VIII) 37598 [4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-2-(hydroxymethyl)phenyl](4-fluorophenyl)methanone C19H18FNO3 详情 详情
(IX) 37604 bromo[3-(dimethylamino)propyl]magnesium 120615-47-6 C5H12BrMgN 详情 详情
(X) 37599 4-(dimethylamino)-1-[4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-2-(hydroxymethyl)phenyl]-1-(4-fluorophenyl)-1-butanol C24H31FN2O3 详情 详情
(XI) 55284 sodium 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carboxylate C20H21FNNaO3 详情 详情
(XII) 55285 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonyl chloride C20H21ClFNO2 详情 详情
(XIII) 55286 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carboxamide C20H23FN2O2 详情 详情
Extended Information