Pivalic acid → HCID 13476231, compound

Participants

Reaction Steps

Into a glass vessel under nitrogen at ambient temperature with stirring was charged a solution of triethylborane in heptane (49.4 ml, 52.5 mmole; 15 percent w/w) and pivalic acid (255 mg, 2.5 mmole). After 90 minutes, methyl (E)-7-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)-5-hydroxy-3-oxo-6-heptenoate (19.2 g, 50.0 mmole) was charged and then dry tetrahydrofuran (170 ml) was added. After 60 minutes, the solution was cooled to -78° C. and methanol (45 ml) was added dropwise. Sodium borohydride (1.42 g, 37.5 mmole) was carefully added in three equal portions at less than -70° C. The reaction mixture was stirred at -78° C. for 2 hours and additional sodium borohydride (472 mg, 12.5 mmole) was added. After 1 hour, the cold reaction mixture was quenched by addition to 30 percent aqueous hydrogen peroxide (200 ml) while maintaining the temperature below 25° C. After 1 hour, ethyl acetate (300 ml) and water (100 ml) were added. The phases were separated and the aqueous phase was washed with ethyl acetate (50 ml). The combined organic phases were washed with 0.5M aqueous hydrochloric acid (300 ml) and then water (3×300 ml). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the product with 98.2 percent of the desired stereochemical conformation.

Provenance & Evidence