Hydrochloric Acid → HCID 57512939, compound

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).

1. stirringThe mixture was stirred at RT overnight
2. extractionThe mixture was extracted into ether
3. washwashed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated
6. dissolutionThe resulting residue was dissolved in 1 L of warm hexane
7. additiontreated with several grams of silica gel
8. customto remove colored impurities
9. filtrationThe resulting mixture was then filtered
10. concentrationthe filtrate was concentrated
11. temperaturechilled in an ice bath for 30 minutes
12. customThe resulting solid was isolated by filtration

ORD record

ord-ee561f99b50040f0849a1b013cc146bc

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754099B2