4-Methylmorpholine → Tert-butyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate

Participants

Reaction Steps

N-methylmorpholine (0.2 mL, 1.8 mmol) was added to a solution of 1-(tert-butoxycarbonyl)-4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]proline (175 mg, 0.40 mmol), 1-amino-4,4-dimethylhexan-2-ol (58 mg, 0.40 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (92 mg, 0.48 mmol), and hydroxybenzotriazole (65 mg, 0.48 mmol) in dichloromethane (40 mL). After stirring at ambient temperature overnight, the reaction mixture was washed with saturated aqueous sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated in vacuo to afford tert-butyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}-pyrrolidine-1-carboxylate which was used in the subsequent step without further purification.

Provenance & Evidence