Triethylamine → (1S,2S)-2-amino-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

Participants

Reaction Conditions

Reaction Steps

Step I (3): Preparation of tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)piperidine-1-carboxylate. To a solution of (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one (Preparation M, 2.2 g, 6.57 mmol) in CH2Cl2 (100 mL) at −78° C. was added Bu2BOTf (di-n-butylboron triflate) (7.9 ml, 7.9 mmol, 1M in CH2Cl2) and triethyl amine (1.4 mL, 10 mmol). The resulting mixture was brought up to 0° C. and stirred for 20 min. The mixture was cooled back to −78° C. and a solution of tert-butyl 2-formylpiperidine-1-carboxylate (Step I (2), 1.4 g, 6.57 mmol) in CH2Cl2 (100 mL) was added. When the addition was complete, the mixture was allowed to warm to and stirred at rt overnight. MeOH was added and the mixture was concentrated in vacuo. The crude mixture was purified by silica gel Flash chromatography to give 2.0 g of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.42-1.66 (14H, m), 1.86-2.26 (1H, m), 2.62-3.40 (6H, m), 3.84-4.69 (7H, m), 6.58-6.65 (1H, m), 6.81-6.85 (2H, m), 6.90-6.96 (2H, m), 7.22-7.27 (3H, m). MS (ESI) (M+Na)+ 581.12.

Provenance & Evidence