1,4-Dioxane hydrochloride → 3-chloro-4-({[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]carbonyl}amino)benzoic acid
Reaction equation
C(OC([N:8]([CH2:21][CH:22]1[CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[CH2:26][CH2:25][N:24]([C:35]([NH:37][C:38]2[CH:46]=[CH:45][C:41]([C:42]([OH:44])=[O:43])=[CH:40][C:39]=2[Cl:47])=[O:36])[CH2:23]1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=O)(C)(C)C.Cl.O1CCOCC1>>[Cl:47][C:39]1[CH:40]=[C:41]([CH:45]=[CH:46][C:38]=1[NH:37][C:35]([N:24]1[CH2:25][CH2:26][CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[CH:22]([CH2:21][NH:8][C@@H:9]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH2:23]1)=[O:36])[C:42]([OH:44])=[O:43]Participants
3
Reactant 2
Product 1
Procedure
To 274 mg of 4-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]carbonyl}amino)-3-chlorobenzoic acid was added 3.0 mL of a 4 M hydrogen chloride/1,4-dioxane solution, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and chloroform and a saturated aqueous sodium hydrogen carbonate solution were added thereto, followed by stirring, separating, and then drying over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol-chloroform) to obtain 157 mg of 3-chloro-4-({[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]carbonyl}amino)benzoic acid as a colorless amorphous substance. The obtained amorphous substance was dissolved in chloroform, and hexane was added thereto to precipitate a white solid, which was collected by filtration to obtain 136 mg of 3-chloro-4-({[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]carbonyl}amino)benzoic acid as a white solid.