2,2,6,6-Tetramethylpiperidine → 2-[2-(S)-[Bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-pyrrole-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Add n-butyllithium (3.30 mL, 8.25 mmol, 2.5 M in hexanes) to a solution of 2,2,6,6-tetramethylpiperidine (1.40 mL, 8.18 mmol) in tetrahydrofuran (THF) (30 mL) at −78° C. over 2 min. Stir 5 min, then warm to −10° C. and stir 5 min, then cool to −78° C. Add N-tert-butoxycarbonylpyrrole (1.37 mL, 8.25 mmol) in THF (1.6 mL) over 3 min. Stir 30 min and add 2-(S)-[bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-propionaldehyde (2.96 g, 7.44 mmol) in THF (15 mL) over 5 min. Stir 60 min at −78° C., warm to 0° C. and stir 60 min. Cool −78° C. and quench with saturated aqueous ammonium chloride solution. Extract with ethyl acetate, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and dichloromethane) to give the title compound as a foam (0.416 g, 10%).

Provenance & Evidence