Methyl 2-chloro-6-methoxyisonicotinate → 2-(1-Ethylpropyl)-6-methoxyisonicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Under argon, Pd(dppf) (83 mg, 101 μmol) is added to a solution of 2-chloro-6-methoxy-isonicotinic acid methyl ester (2.00 g, 9.92 mmol, see preparation of 2-isobutyl-6-methoxy-isonicotinic acid) in dioxane (30 mL). To this mixture, a solution of 1-ethyl-propyl zinkbromide (1.17 g, 9.92 mmol, 20 mL of a 0.5 M solution in THF) is added. The mixture is stirred at 85° C. for 16 h before the reaction is carefully quenched with water and extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid methyl ester (1.17 g) as a pale yellow oil; LC-MS: tR=1.08 min; [M+1]+=238.03.

Provenance & Evidence