Ammonium Chloride → 1-(5-Methyl-2-pyridinyl)ethanone

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-bromo-5-methylpyridine 23 (1.73 g, 10 mmol) in dry ether (20 ml), cooled to −78° C., was added n-butyllithium (6.25 ml of 1.6M solution in hexanes, 10 mmol, 1 equiv) dropwise. The reaction mixture was allowed to warm to −40° C. for 15 min, then cooled back to −78° C. again. N,N-dimethylacetamide (1.023 ml, 11 mmol, 1.1 equiv) was added dropwise and the mixture was stirred at −78° C. for 2 h. Saturated aqueous ammonium chloride (10 ml) was added and the organic layer was separated. The aqueous layer was extracted with ether (3×10 ml) and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give an oily residue that was subjected to flash column chromatography using (5% methanol in methylene chloride) to give compound 25 (0.977 g, 72%) as a yellow oil: TLC Rf=0.48 (silica gel, 25% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 8.5-8.48 (broad s, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.63-7.60 (m, 1H), 2.70 (s, 3H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 200.2, 151.7, 149.7, 137.8, 137.4, 121.7, 26.0, 18.9; HRMS calcd for C8H9NO+Na+ 158.0582; found 158.0580 [M+Na+].

Provenance & Evidence