Reaction Steps
A mixture of potassium ferricyanide (21 mg, 0.06 mmol), potassium carbonate (8.9 mg, 0.06 mmol), and (DHQ)2PHAL (0.3 mg, 3%) was treated with a solution of water/tert-butyl alcohol (5 mL, 1:1) and stirred at 25° C. for 5 min (until clear solution obtained). The reaction mixture was treated with a 0.2 M solution of osmium tetroxide in toluene (1μ, 1%) and cooled to 0° C. To this was added 2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(3-methyl-but-2-enyl)-1H-pyrazol-3-yl]-propionamide (prepared as in Example 51, 10 mg, 0.022 mmol) and methane sulfonamide (2 mg, 0.02 mmol). The heterogeneous mixture was stirred at 0° C. for 20 h. After such time the cooling bath was removed and the mixture was treated while stirring with ethyl acetate (15 mL) and sodium sulfite (50 mg, 0.39 mmol). To this solution was added water (20 mL) and the phases were separated. The aqueous phase was backextracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification an AnaLogix Intelliflash system (4 g column, 70% ethyl acetate/hexanes to 100% ethyl acetate) afforded (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2,3-dihydroxy-3-methyl-butyl)-1H-pyrazol-3yl]propionamide (6.7 mg, 63%) as a single diastereomer of unknown stereochemistry at the hydroxyl carbon center: [α]29589=−10.2° (c=0.48, methanol); ES-HRMS m/e calcd for C23H32ClN3O5S (M+H)+ 498.1824, observed 498.1824; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.05 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.11 (m, 2H, CH2) 1.39-1.79 (m, 8H, 4×CH2), 2.10 (m, 1H, CH), 3.34 (s, 3H, SO2CH3), 3.46 (m, 1H, OCH), 3.75 (dd, J=9.6 Hz, 13.5 Hz, 1H, NCH of NCH2), 3.90 (m, 1H, ArCHCO), 4.21 (d, J=13.5 Hz, 1H, NCH of NCH2), 4.42 (s, 1H, OH), 4.82 (d, J=6.3 Hz, 1H, OH), 6.39 (d, J=2.3 Hz, 1H, Ar), 7.51 (d, J=2.3 Hz, 1H, Ar), 7.59 (dd, Jo=8.3, Jm=1.6 Hz, 1H, Ar), 7.70 (d, Jm=1.6 Hz, 1H, Ar), 8.01 (d, Jo=8.3 Hz, 1H, Ar), 10.78 (s, 1H, NH).
