Hydrochloric Acid → HCID 86749412, compound

Participants

Reaction Conditions

Reaction Steps

Methyl acetoacetate (160 mg, 1.38 mmol) was dropwise to a slurry of NaH (60% in mineral oil, 55.1 mg, 1.38 mmol) in dry THF (3.5 ml) at 0° C. After 15 minutes, n-BuLi (1.5M in hexane, 830 ul, 1.25 mmol) was added and the mixture was stirred an additional 15 minutes. The bright yellow solution was cooled to -78° C. and treated with a solution of (E)-3-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-2-propenal (317 mg, 0.92 mmol) in THF (2 ml). Stirring continued for 20 minutes, after which time the reaction was warmed to 0° C. and stirred for an additional 20 minutes. The yellow-orange solution was then added to a biphasic mixture of 1N HCl (3 ml), H2O (15 ml), and Et2O (30 ml). The aqueous layer was made slightly basic with saturated NaHCO3 and the phases were separated. The aqueous layer was diluted with saturated NH4Cl and was extracted with Et2O once again. The combined organic layers were washed with brine and dried (Na2 SO4). Filtration and removal of the solvent afforded an oil which was chromatographed (flash, Merck SiO2, 35% EtOAc in hexane) to give (E)-7-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester as an oily solid (187 mg, 44%).

Provenance & Evidence