Nicotinic Acid → 2-[Cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-3-oxo-3-pyridin-3-yl-propionic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To solution of 12.7 ml (1 M in THF, 13 mmol) of lithium hexamethyldisilylazide cooled to −78° C. under Ar was added, drop wise, a solution of 3.8 g (12 mmol) of [cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-acetic acid ethyl ester (intermediate 7B) in 20 ml of THF. The mixture was brought to −30° C. and stirred for 1 h. Separately, 0.6 g (5 mmol) of nicotinic acid was added to 0.8 g (5 mmol) of 1,1-carbonyl diimidazole in 10 ml of CH2Cl2 and the mixture stirred for 1 h after which time it was concentrated to dryness. The crude residue was re-dissolved in 10 ml of THF under Ar and cooled to −30° C. The enolate solution of intermediate 7B (described above) was then added by cannula to the crude imidazolide solution and the mixture was allowed to reach room temperature. After 2 h the reaction was diluted with EtOAc, washed with saturated ammonium chloride solution, the organic phase dried with sodium sulfate and concentrated. Purification by flash column chromatography [n-heptane/EtOAc 1:1] afforded 1.2 g (58%) of the title compound as an orange oil. MS: 437.2 (MH+).

Provenance & Evidence