Dimethyl Sulfoxide → HCID 86598720, compound

Participants

Reaction Conditions

Reaction Steps

A solution of the product of Example 61B (2.26 g) in dichloromethane (20 mL) was treated with oxalyl chloride (5.4 mL, 1.5 equivalents) at −78° C., and stirred for 15 min. DMSO (1.02 mL, 2 equivalents) was added dropwise at −78° C., stirred for 15 min, and quenched with triethylamine (4 mL, 4 equivalents) as the mixture warmed to 0° C. The mixture was quenched with 20% KH2PO4, and partitioned between dichloromethane and water. The organic layer was washed with brine, dried over Na2SO4, and the solvents were evaporated. To this crude product was added methanol/water (7:2), (L)-valine methyl ester (1.21 g, 1 equivalent), sodium acetate trihydrate (1.96 g, 2 equivalents), and NaCNBH3 (0.95 g, 2 equivalents) was added portionwise over 30 min. After stirring for 1 hour, the mixture was partitioned between saturatued NaHCO3, and extracted with ethyl acetate (2×). The combined organic layer was washed with brine, dried with Na2SO4, filtered, and evaporated. The residue was treated with dichloromethane/trifluoacetic acid (10 mL, 1:1), stirred at 25° C. for 2 hrs and concentrated to give the title compound isolated as the trifluoroacetic acid salt.

Provenance & Evidence