Diisopropylamine → HCID 67606381, compound

Participants

Reaction Conditions

Reaction Steps

To generate LDA: To a chilled (ice-acetone bath) solution of diisopropylamine (5.1 mL, 36 mmol) in dry THF (30 mL) was added n-BuLi (1.45 M solution in hexanes, 24 mL, 35 mmol) drop-wise and under an atmosphere of nitrogen. The solution was stirred for 15 minutes before being added to a suspension of 3-methylpyridine-2-carboxylic acid (1.5 g, 11 mmol) in THF (50 mL) drop-wise, at −78° C. and under an atmosphere of nitrogen. The dark purple mixture was stirred at −78° C. for 30 minutes and then at −5° C. for 30 minutes. After this time the mixture was re-cooled to −78° C. and a solution of methyl 4-fluorobenzoate (1.6 mL, 12 mmol) in THF (15 mL) was added. The dark brown mixture was stirred at −78° C. for 1.5 hours and then at 0° C. for 2.5 hours. The mixture was then poured into chilled water (50 mL) and washed with ethyl acetate (3×35 mL). The aqueous layer was acidified to pH 2 with HCl and extracted with ethyl acetate (3×75 mL). The three extracts were combined and concentrated in vacuo to yield 3-[2-(4-fluorophenyl)-2-oxoethyl]pyridine-2-carboxylic acid as a pale yellow solid (1.5 g, 53% yield). ESI-MI m/z [M+H]+ 259.95. 1H NMR (400 MHz, DMSO) δ 8.61 (dd, J=4.7, 1.6 Hz, 1H), 8.14 (dd, J=8.9, 5.5 Hz, 2H), 7.86 (dd, J=7.8, 1.6 Hz, 1H), 7.62 (dd, J=7.7, 4.7 Hz, 1H), 7.40 (t, J=8.9 Hz, 2H), 4.78 (s, 2H).

Provenance & Evidence