Lithium borohydride → 4-chloro-N-[(1S)-4,4,4-trifluoro-1-hydroxymethyl-2-(2,2,2-trifluoroethyl)-butyl]benzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

To a solution of (2S)-2-(4-chloro-benzenesulfonylamino)-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)pentanoic acid methyl ester (2.924 g, 6.6 mmol) in THF (30 mL) was added LiBH4 (9.9 mL of 2M THF solution, 19.8 mmol) over 10 minutes at 4-6° C. The reaction mixture was stirred at 25° C. for 4 days. Additional LiBH4 (6.6 mL of 2M THF solution, 13.2 mmol) was added, and the reaction mixture was stirred at 25° C. for an additional 24 hours. The reaction mixture was cooled to 0° C. and quenched by slow addition of 30 mL of 2N HCl (vigorous gas evolution). The mixture was partially concentrated in vacuum and extracted with EtOAc. The organic fraction was washed with brine, dried over Na2SO4, and concentrated to afford 2.66 g of crude product. The crude product was dissolved in a mixture of EtOAc (10 mL) and heptane (3 mL) at 55° C., cooled to 25° C., and the resultant suspension was aged for 48 hours. Heptane (27 mL) was added and the mixture was stirred at 25° C. for additional 48 hours. The precipitate was filtered and washed with heptane to afford 1.962 g of the title compound (72% yield), mp: 186-187° C. Chiral HPLC: 97% ee (the Chiralcel® AD column 0.46×25 cm, 10% EtOH in hexanes). HRMS calc. (for M+H): 414.0360. Found: 414.0359.

Provenance & Evidence