反应详情

A solution of (E)-7-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester (357 mg, 0.77 mmol) in THF (12 ml) was treated with triethylborane (1.0M in THF, 1.62 ml, 1.62 mmol). Twenty five milliliters of air was bubbled through the solution and the mixture was stirred at room temperature for 30 minutes. The solution was cooled to -78° C. and treated with NaBH4 (29.4 mg, 0.78 mmol) followed by dropwise addition of dry methanol (1.90 ml). After stirring at -78° C. for 1.5 hours, the mixture was quenched with 30% H2 O2 (3.5 ml) in H2O (11 ml). The mixture was kept at -78° C. for 15 minutes, then warmed to room temperature and stirred for 30 minutes. The solution was poured into 50% saturated NaHCO3 and extracted with Et2O (3×). The Et2O extracts were combined, washed with H2O, saturated NaHCO3 and brine, then dried (Na2SO4). Filtration and removal of the solvent gave a yellow oil which was chromatographed (Flash, Merck SiO2, 40% EtOAc in hexane) to afford (3R, 5S, 6E)-7-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]3,5-dihydroxy-6-heptenoic acid, methyl ester (320 mg, 89%) as a colorless oily foam.

1. customTwenty five milliliters of air was bubbled through the solution
2. temperatureThe solution was cooled to -78° C.
3. stirringAfter stirring at -78° C. for 1.5 hours
4. customthe mixture was quenched with 30% H2 O2 (3.5 ml) in H2O (11 ml)
5. waitThe mixture was kept at -78° C. for 15 minutes
6. temperaturewarmed to room temperature
7. stirringstirred for 30 minutes
8. additionThe solution was poured into 50% saturated NaHCO3
9. extractionextracted with Et2O (3×)
10. washwashed with H2O, saturated NaHCO3 and brine
11. dry with materialdried (Na2SO4)
12. filtrationFiltration and removal of the solvent
13. customgave a yellow oil which
14. customwas chromatographed (Flash, Merck SiO2, 40% EtOAc in hexane)