Tetrahydrofuran → 5-ethoxy-carbonylmethylidene-7-chloro-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine

반응식

[H-].[Na+].[CH2:3]([O:5]P(CC(OCC)=O)(OCC)=O)[CH3:4].[O:17]=[C:18]1[C:24]2[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=2[N:22]([C:30](=[O:48])[C:31]2[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:46])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH3:45])=[CH:33][C:32]=2[CH3:47])[CH2:21][CH2:20][CH2:19]1.O1CC[CH2:51][CH2:50]1>>[CH2:50]([O:17][CH:18]1[C:24]2[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=2[N:22]([C:30](=[O:48])[C:31]2[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:46])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH3:45])=[CH:33][C:32]=2[CH3:47])[C:21](=[C:4]=[C:3]=[O:5])[CH2:20][CH2:19]1)[CH3:51]

참가 물질

반응물 4

HCID 8028Tetrahydrofuran

HCID 13345Triethyl phosphonoacetate

HCID 24758Sodium hydride

HCID 113628435-Dehydro Tolvaptan

생성물 1

HCID 867507475-ethoxy-carbonylmethylidene-7-chloro-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine

실험 절차

0.85 g of 60% sodium hydride was added to 200 ml of tetrahydrofuran. Thereto was dropwise added 4.68 ml of ethyl diethylphosphonoacetate with ice-cooling and stirring. The mixture was stirred for 10 minutes with ice-cooling. To the reaction mixture was added 2.10 g of 5-oxo-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)-benzoyl]-2,3,4,5-tetra-hydro-1H-benzoazepine. The mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into 200 ml of ice water. The resulting mixture was subjected to extraction with 300 ml of ethyl acetate. The extract was washed with 300 ml of an aqueous sodium chloride solution, then dried over magnesium sulfate, and subjected to distillation to remove the solvent. The residue was purified by silica gel column chromatography (elutant: ethyl acetate/n-hexane =1/2) to obtain 2.22 g of 5-ethoxy-carbonylmethylidene-7-chloro-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-benzoazepine as a mixture of the E form and the Z form.