Dimethyl oxalate → HCID 178501823, compound

2′-chloro-6′-fluoro-3′-methylacetophenone (1.00 g, 5.36 mmol) was dissolved in 2.0 mL anhydrous methanol under N2 and subjected to the addition of 25% sodium methoxide in methanol (2.2 equiv, 11.8 mmol, 2.7 mL) via syringe. The nearly colorless solution was stirred for 30 min and then dimethyl oxalate (2.2 equiv, 11.8 mmol, 1.39 g) was added. The cloudy white mixture was stirred at 30° C. After 15 h, the cloudy white mixture was quenched with 2.0 mL 2 M HCl(aq) and extracted with 3×10 mL EtOAc. The light yellow organics were washed with 10 mL saturated brine solution, dried over anhydrous MgSO4 for 5 min, filtered, and concentrated in vacuo to afford a light yellow solid. Silica gel chromatography followed by recrystallization from hot hexanes/dichloromethane (ca. 5:1) afforded the desired product as analytically pure white needles (688 mg, 47% yield).

1. stirringThe cloudy white mixture was stirred at 30° C
2. waitAfter 15 h
3. customthe cloudy white mixture was quenched with 2.0 mL 2 M HCl(aq)
4. extractionextracted with 3×10 mL EtOAc
5. washThe light yellow organics were washed with 10 mL saturated brine solution
6. dry with materialdried over anhydrous MgSO4 for 5 min
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto afford a light yellow solid
10. customSilica gel chromatography followed by recrystallization from hot hexanes/dichloromethane (ca. 5:1)

ORD record

ord-8ade4a13881e420b9c131a96c401889b

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664255B2