Ammonium Chloride → HCID 49762692, compound

Under an argon gas flow, half of a solution of 4-bromobenzotrifluoride (1.20 g, 5.33 mmol) in THF (6 mL) was added to magnesium (156 mg, 6.41 mmol). The resulting solution was stirred, and further 1,2-dibromoethane (3 drops) was added. Once the reaction began, the balance of the 4-bromobenzotrifluoride in THF solution was added dropwise, and once dropping had finished, the resulting solution was stirred for 30 minutes at 60° C. A solution of 6-chloro-N-methoxy-N-methylnicotinamide (990 mg, 5.36 mmol) in THF (3 mL) was charged into a separate reaction vessel, into which the above reaction solution was added dropwise under an argon gas flow and ice cooling. After dropping had finished, the resulting solution was stirred for 30 minutes at room temperature, and then heated to reflux for 1 hour. The reaction solution was cooled with ice, then aqueous ammonium chloride and water were added. The resulting solution was extracted with ethyl acetate, and washed with brine. The ethyl acetate layer was dried over anhydrous magnesium sulfate, evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), to thereby yield 610 mg of the title compound.

1. stirringthe resulting solution was stirred for 30 minutes at 60° C
2. additionwas added dropwise under an argon gas flow and ice cooling
3. stirringthe resulting solution was stirred for 30 minutes at room temperature
4. temperatureheated
5. temperatureto reflux for 1 hour
6. temperatureThe reaction solution was cooled with ice
7. extractionThe resulting solution was extracted with ethyl acetate
8. washwashed with brine
9. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
10. customevaporated
11. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1)

ORD record

ord-8ae8bd35699a4f568308ddae3bd09233

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236826B2