Tributylphosphine → 5-(R)-[1-(S)-benzyloxy-2-(S)-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester

Participants

Reaction Steps

Dissolve [2-(S)-benzyloxy-3-(S)-dibenzylamino-4-(3,5-difluorophenyl)-1-(R)-hydroxymethylbutyl]-(2-(S)-hydroxy-5-methylhexyl)-carbamic acid tert-butyl ester (253 mg, 347 mmol) in benzene (3 mL). Deoxygenate the reaction mixture. Add tributyl phosphine (130 μL, 520 mmol), N,N-tetramethyl azodicarboxamide (TMAD) (89.5 mg, 520 mmol) and stir at room temperature 2.5 hours. Add deoxygenated tetrahydrofuran (5 mL), more tributyl phosphate (130 μL), more TMAD (90 mg) and stir 1.5 hours. Filter, rinse with hexanes, concentrate and purify (silica gel chromatography, eluting with 5:95 ethyl acetate:hexanes) to give the desired compound (191.7 mg, 77%).

Provenance & Evidence