Hydrogen Peroxide → HCID 131729391, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (3R,4S,5S)-3-[(R)-1-(3-tert-butyl-phenyl)-ethylamino]-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-tetrahydro-thiopyran-4-ol (0.249 g, 0.423 mmol) in THF (2 mL) and AcOH (1 mL) was treated with 0.22 mL 30% H2O2 and stirred for 18 h at 25° C. The mixture was diluted with EtOAc and washed with aq. Na2S2O3, and brine. The organic layer was dried over Na2SO4 and evaporated to give (3R,4S,5S)-3-[(R)-1-(3-tert-butyl-phenyl)-ethylamino]-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-1-oxo-hexahydro-1lambda*4*-thiopyran-4-ol as a mixture of sulfoxide diastereomers (HPLC RtH1=2.30, 2.39 min; ESIMS [M+H]+=605), pure enough for further transformation. This product was dissolved in THF-MeOH 4:1 (5 mL) and stirred in the presence of 10% Pd—C (0.1 g) under an atmosphere of hydrogen at 45° C. for 1.5 h. The mixture was filtered over Celite, evaporated and dissolved in 5 mL 3N HCl in MeOH. After 3 d the reaction mixture was concentrated and taken up in 10% aq. Na2CO3 solution and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered and evaporated. The title compound was obtained after purification by column chromatography on silica gel (EtOAc/5% MeOH) 70-0% hexane as a colorless foam: HPLC RtH1=2.535 min; ESIMS [M+H]+=575; [α]D=−9.8° (c=0.4, CH2Cl2); 1H NMR (600 MHz, DMSO-d6): δ 7.37 (s, 1H), 7.23-7.20 (m, 2H), 7.13 (m, 1H), 6.69 (s, 1H), 6.61 (d, 1H), 5.10 (m, 1H), 4.82 (s, OH), 4.59-4.55 (NH2), 3.80 (m, 1H), 3.70 (m, 2H), 3.30 (s, 3H), 3.23 (d, 1H), 3.02 (m, 1H), 2.92 (m, 1H), 2.80 (m, 1H), 2.62 (m, 1H), 2.39 (m, 1H), 2.25-2.18 (m, 3H), 1.25 (s, 9H), 1.20 (d, 3H).

Provenance & Evidence