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【结 构 式】 
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【分子编号】10056 【品名】6-Fluoro-2,3-dihydro-4H-chromen-4-one; 6-Fluoro-4-chromanone 【CA登记号】66892-34-0 |
【 分 子 式 】C9H7FO2 【 分 子 量 】166.1517832 【元素组成】C 65.06% H 4.25% F 11.43% O 19.26% |
合成路线1
该中间体在本合成路线中的序号：(III)The synthesis of [2H]-, [3H]- and [14C]-radiolabeled sorbinil has been described: [2H]- and [3H]-sorbinil are prepared by chlorination of sorbinil (I) with Cl2 and FeCl2 in dry DMF to give the 8-chloro derivative (II), which is then reduced with deuterium or tritium over Pd/C in ethanol. [14C]-Labeled sorbinil is prepared by cyclization of 6-fluoro-3,4-dihydro-2H-benzo[b]pyran-4-one (III) with [14C]-potassium cyanide and ammonium carbonate in hot ethanol-water to give radiolabeled racemic sorbinil, which is then submitted to optical resolution with brucine in ethanol.
| 【1】 Howard, H.R.; Sarges, R.; Evans, M.; Synthesis of H-2-labelled, H-3-labelled and C-14-labelled CP-45,634 (sorbinil). J Label Compd Radiopharm 1991, 29, 6, 703. |
| 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) | 10054 | (S)-6-Fluorospiro(chroman-4,4'-imidazolidine)-2',5'-dione | 68367-52-2 | C11H9FN2O3 | 详情 | 详情 |
| (II) | 10055 | (S)-8-Chloro-6-fluorospiro(chroman-4,4'-imidazolidine)-2',5'-dione | C11H8ClFN2O3 | 详情 | 详情 | |
| (III) | 10056 | 6-Fluoro-2,3-dihydro-4H-chromen-4-one; 6-Fluoro-4-chromanone | 66892-34-0 | C9H7FO2 | 详情 | 详情 |
| (IV) | 10057 | 6-Fluorospiro[chroman-4,4'-imidazolidine]-2',4'-dione | 69684-83-9 | C11H9FN2O3 | 详情 | 详情 |
| (IV) | 44570 | C11H9FN2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)A new method for the synthesis of sorbinil has been reported: The condensation of 2,3-dihydro-6-fluoro-4H-1-benzopyran-4-one (I) with methylbenzylamine (II) by means of TiCl4 in benzene gives 2,3-dihydro-6-fluoro-4-(1-phenylethylimino)-4H-1-benzopyran (III), which by reaction with HCN in ethanol is converted to 4-cyano-2,3-dihydro-6-fluoro-4-(1-phenylethylamino)-4H-1-benzopyran (IV). The cyclization of (IV) with chlorosulfonyl isocyanate (V) in methylene chloride affords 2,3-dihydro-6-fluoro-3'-(1-phenylethyl)spiro(4H-1-benzopyran-4,4'-imidazolidine)-2',5'-dione (VI), which is finally treated with 48% HBr in refluxing acetic acid.
| 【1】 Kelbaugh, P.R.; Sarges, R.; Howard, H.R. Jr.; Synthesis of optically active spirohydantoins by asymmetric induction. Hydantoin formation from amino nitriles and chlorosulfonyl isocyanate. J Org Chem 1982, 47, 21, 4081-85. |
| 【2】 Sarges, R. (Pfizer Inc.); Intermediates in the preparation of chiral hydantoins. US 4348526 . |
| 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) | 10056 | 6-Fluoro-2,3-dihydro-4H-chromen-4-one; 6-Fluoro-4-chromanone | 66892-34-0 | C9H7FO2 | 详情 | 详情 |
| (II) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (III) | 29153 | N-(6-fluoro-2,3-dihydro-4H-chromen-4-ylidene)-1-phenyl-1-ethanamine | C17H16FNO | 详情 | 详情 | |
| (IV) | 29154 | 6-fluoro-4-[(1-phenylethyl)amino]-4-chromanecarbonitrile | C18H17FN2O | 详情 | 详情 | |
| (V) | 14101 | Chlorosulfonyl isocyanate | 1189-71-5 | CClNO3S | 详情 | 详情 |
| (VI) | 29155 | (4S)-6-Fluoro-3'-(1-phenylethyl)-3,4-dihydro-2H-spiro[1-benzopyran-4-4'-imidazolidine]-2',5'-dione | C19H17FN2O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The cyclization of 3-(p-fluorophenoxy)propionic acid (I) with polyphosphoric acid in boiling water gives 6-fluoro-4-chromanone (II), which is then treated with KCN and ammonium carbonate in hot ethanol-water.
