Ethanol → Ethyl 5-fluoropyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a Parr shaker add 2-bromo-5-fluoropyridine (Example 382, Part A) (7.00 g, 39.8 mmol), NaOAc (13.1 g, 159 mmol), absolute ethanol (100 mL) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II):dichloromethane (1.62 g, 1.99 mmol). Charge the reaction vessel with 50 psi of CO. Heat at 90° C. for 18.25 hours. Cool the reaction mixture before filtering through a Celite® pad. Wash the pad with ethyl acetate, then concentrate the filtrate. Purify by flash chromatography, eluting with 25% ethyl acetate in hexanes to give the title compound (4.62 g, 68.6%): MS ES+ 169.9 (M+H)+, base peak MS ES+ 141.8 (M+H—CH2CH3)+; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.10% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=10.3 min, 97.0 purity.

Provenance & Evidence