Potassium Carbonate → 4-Bromo-3-fluoro-N-methoxy-N-methylbenzamide

Oxalyl chloride (38.1 mL, 450 mmol) was slowly added to a mixture of 4-bromo-3-fluorobenzoic acid (49.3 g, 225 mmol) (Alfa Aesar, Cat. # B25475) in dichloromethane (300 mL). Subsequently, N,N-dimethylformamide (1.0 mL) was added and the reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was concentrated under reduced pressure and co-evaporated with toluene 3 times. The residue was then dissolved in dichloromethane (100 mL). The solution was added drop-wise to a mixture of N,O-dimethylhydroxylamine hydrochloride (30.7 g, 315 mmol) and potassium carbonate (120 g, 900 mmol) in dichloromethane (300 mL) and water (300 mL). The reaction mixture was stirred at ambient temperature for 2 hours. The organic layer was separated. The aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the product. (58.5 g) LCMS (M+H)+: m/z=261.9/263.9.

1. concentrationThe reaction mixture was concentrated under reduced pressure and co-evaporated with toluene 3 times
2. dissolutionThe residue was then dissolved in dichloromethane (100 mL)
3. additionThe solution was added drop-wise
4. stirringThe reaction mixture was stirred at ambient temperature for 2 hours
5. customThe organic layer was separated
6. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
7. washThe combined organic extracts were washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto give the product

ORD record

ord-4b99b863ebab412591a9213192b30a4f

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487096B2