A mixture of (2S,3S,5S)-5-hydroxy-3-(methoxycarbonyl)piperidine-2-carboxylic acid (0.309 g, 0.00152 mol), 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (0.357 g, 0.00182 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.807 g, 0.00182 mol) in N,N-dimethylformamide (2.50 mL, 0.0323 mol) was stirred at rt for 5 min, then treated with N,N-diisopropylethylamine (0.636 mL, 0.00365 mol) at rt for 2 h. The reaction mixture was diluted with acetonitrile (5.0 mL, 0.096 mol) and tetrahydrofuran (5.0 mL, 0.062 mol). To the mixture was added 12.32 M of formaldehyde in Water (0.41 mL) followed by sodium triacetoxyborohydride (1.1 g, 0.0051 mol). After stirred at rt overnight, the mixture was concentrated to dry, then diluted with aq. sodium bicarbonate, extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated to dry. The residue was applied on silica gel, eluting with 0 to 100% EtOAc in hexane, to yield the methyl amine compound (0.31 g, 85%). MS (ESI): (M+H)+=358.1.
