Potassium bisulfate → [(3R*,4R*,5S*)-5-(3-Fluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of calcium borohydride bis-THF complex (1.14 g, 4.6 mmol) in anhydrous THF (100 mL) was added under argon a solution of [(3R*,5S*)-5-(3-fluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester (1.77 g, 4.6 mmol) in THF (50 mL) at −70° C. The reaction mixture was slowly warmed to −40° C. and stirred for 1 h at −40° C. The reaction mixture was poured onto a cold aq. KHSO4 solution and the product was extracted with EtOAc. Combined extracts were washed with NaHCO3 solution and brine, dried over MgSO4 and evaporated. The mixture of diastereoisomers was separated by flash-chromatography on silica gel (toluene-EtOAc 6:1 to 3:1) to yield the undesired [(3R*,4S*,5S*)-diastereoisomer and the desired [(3R*,4R*,5S*)-diastereoisomer after crystallization from EtOH as a white crystalline solid: TLC (toluene-EtOAc 3:1) Rf=0.20; HPLC RtA=1.94 min; ESIMS [M+H-isobutylene]+=331; 1H NMR (600 MHz, DMSO-d6): δ 8.09 (t, 1H), 7.41 (d, 1H), 7.27 (d, 1H), 6.67 (d, 1H), 4.94 (d, 1H), 3.42 (m, 1H), 3.27 (dd, 1H), 2.91 (m, 1H), 2.55 (m, 2H), 2.39 (dd, 1H), 2.24 (m, 2H), 1.93 (m, 1H), 1.37 (s, 9H).

Provenance & Evidence