Dichloromethane → (S)-4-methyl-2-(methylamino)pentanoic acid [4,4-bis(4-fluorophenyl)butyl]amide hydrochloride
Reaction equation
C(O[C:6](=O)[N:7]([C@H:9]([C:14](=[O:34])[NH:15][CH2:16][CH2:17][CH2:18][CH:19]([C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH2:10][CH:11]([CH3:13])[CH3:12])C)(C)(C)C.FC(F)(F)C(O)=O.C(Cl)[Cl:44]>>[ClH:44].[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH:19]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:18][CH2:17][CH2:16][NH:15][C:14](=[O:34])[C@@H:9]([NH:7][CH3:6])[CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:25][CH:24]=1Participants
4
Procedure
To a solution of (S)-{1-[4,4-bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl}-methyl-carbamic acid tert-butyl ester in CH2Cl2 (15 mL) was added trifluoroacetic acid (5 mL) at ambient temperature under nitrogen atmosphere. The resulting reaction mixture was stirred for 25 minutes, then concentrated in vacuo. The viscous oil obtained was dissolved in 60 mL of CH2Cl2 and successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL), and was dried over Na2SO4. The CH2Cl2 solution of free amine was concentrated in vacuo to afford the crude product as a viscous oil which was further purified by flash chromatography (10% methanol in chloroform). The free amine isolated was dissolved in 10 mL of ethyl ether. To this solution was added saturated HCl solution in ethyl ether until no more white precipitate formed. Filtration and drying overnight under vacuum afforded 0.65 g (89%) of pure titled compound as a white foam: mp 70-84° C. APCI-MS m/z 389.0 (MH+).