Hydrochloric Acid → HCID 57512939, compound

Participants

Reaction Steps

2-Bromo-5-fluoropyridine (50.0 g, 284 mmol) in 200 mL of THF was added dropwise over 25 min to isopropylmagnesium chloride (2 M in THF, 284 mL, 568 mmol) at RT, and the mixture was stirred for 2 hours at room temperature. A solution of 2-chloro-N-methoxy-N-methylacetamide (43.0 g, 313 mmol) in 150 mL of THF was added dropwise over 30 minutes to the reaction mixture at RT. The mixture was stirred at RT overnight. The mixture was then poured into 2000 g of ice with 500 mL of 2 N HCl. The mixture was extracted into ether, washed with brine, dried over anhydrous sodium sulfate and concentrated. The resulting residue was dissolved in 1 L of warm hexane and treated with several grams of silica gel to remove colored impurities. The resulting mixture was then filtered, and the filtrate was concentrated and chilled in an ice bath for 30 minutes. The resulting solid was isolated by filtration to give 2-chloroacetyl-5-fluoropyridine. 1H NMR (500 MHz, CDCl3): δ 8.53 (d, 1H), 8.19 (dd, 1H), 7.60 (td, 1H), 5.09 (s, 2H).

Provenance & Evidence