Hydrochloric Acid → HCID 66933484, compound

Participants

Reaction Conditions

Reaction Steps

Diethyl zink (9.78 g, 79.2 mmol) is added to a solution of 5-bromo-6-methyl-pyridine-2-carboxylic acid isopropyl ester (14.6 g, 56.5 mmol, prepared in analogy to 5-bromo-6-methyl-pyridine-2-carboxylic acid ethyl ester) and Pd(dppf) (461 mg, 0.565 mmol) in dioxane (250 mL). The mixture is stirred at 80° C. for 18 h before it is cooled to rt, diluted with ice-water (150 mL) and EA (250 mL) and acidified with 2 N aq. HCl. The org. layer is separated and the aq. phase is extracted with EA (3×100 mL) and DCM (4×100 mL). The aq. phase is neutralised by adding sat. aq. NaHCO3 solution and is again extracted with DCM (4×75 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane to give 5-ethyl-6-methyl-pyridine-2-carboxylic acid isopropyl ester (7.08 g) as a pale yellow oil; LC-MS: tR=0.77 min, [M+1]+=207.99. 1H NMR (CDCl3): δ 1.25 (t, J=7.5 Hz, 3H), 1.41 (d, J=6.3 Hz, 6H), 2.63 (s, 3H), 2.70 (q, J=7.5 Hz, 2H), 5.30 (hept, J=6.3 Hz, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.87 (d, J=8.0 Hz, 1H).

Provenance & Evidence