Pyridine → N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide

To a stirred mixture of N,O-dimethylhydroxylamine hydrochloride (9.47 g, 97.1 mmol) and pyridine (18.6 mL, 230 mmol) in CH2Cl2 (100 mL) was added a solution of 6-(trifluoromethyl)nicotinoyl chloride (18.50 g, 88.28 mmol) in CH2Cl2 (250 mL) over 3-5 min. The reaction mixture was stirred at rt overnight, and then carefully quenched with 150 mL of saturated aq. NaHCO3 solution and stirred for about 1 hr. The mixture was diluted with CH2Cl2 (50 mL) and the organic phase was separated and washed with aq. NaHCO3 solution (100 mL) and brine (50 mL), dried (Na2SO4), filtered, and evaporated. The residue was redissolved in toluene (about 50 mL) and evaporated again to azeotrope the pyridine off. This was repeated with toluene (about 50 mL). The product was isolated as a colorless oil (with a small amount of crystalline material) (19.1 g, 92%).

1. customcarefully quenched with 150 mL of saturated aq. NaHCO3 solution
2. stirringstirred for about 1 hr
3. additionThe mixture was diluted with CH2Cl2 (50 mL)
4. customthe organic phase was separated
5. washwashed with aq. NaHCO3 solution (100 mL) and brine (50 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated
9. dissolutionThe residue was redissolved in toluene (about 50 mL)
10. customevaporated again
11. customThe product was isolated as a colorless oil (with a small amount of crystalline material) (19.1 g, 92%)

ORD record

ord-1206f6c22a9d4ae69e0bf61162ee6820

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653091B2