Benzylamine → (3S)-1-benzyl-4,4-dimethyl-3-pyrrolidinol
Reaction equation
CS(O[CH2:6][C@@H:7]([OH:17])[C:8]([CH3:16])([CH3:15])[CH2:9]OS(C)(=O)=O)(=O)=O.[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)C>[CH2:18]([N:25]1[CH2:9][C:8]([CH3:16])([CH3:15])[C@H:7]([OH:17])[CH2:6]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 21.7 g (75 mmol) of (2S)-2-hydroxy-3,3-dimethyl-4-[(methylsulfonyl)oxy]butyl methanesulfonate and 24.4 mL (228 mmol) of benzylamine in 200 mL of ethanol was heated at 120° C. for 18 h in a 400 mL capacity bomb. The reaction mixture was allowed to cool to room temperature, the bomb was vented, and the reaction mixture was concentrated under reduced pressure to 100 mL. The reaction was diluted with 50 mL of water and made acidic with concentrated hydrochloric acid. The aqueous phase was then washed with ether, made basic with 5M aqueous sodium hydroxide, and extracted with ether. The ether extract was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 0.25:9.75 2M ammonia in methanol:ethyl acetate to afford 13.8 g (90%) of (3S)-1-benzyl-4,4-dimethyl-3-pyrrolidinol. 1H NMR (300 MHz, CDCl3) δ 7.30-7.36 (m, 5H), 3.77 (br s, 1H), 3.65 (s, 2H), 2.93-2.99 (m, 1H), 2.55-2.64 (m, 2H), 2.31 (d, J=9 Hz, 1H), 1.76 (d, J=7 Hz, 1H), 1.09 (d, J=1 Hz, 6H).