Dimethylformamide → 2-Chloro-4-(methoxymethyl)-6-(trifluoromethyl)pyridine

To a solution of [2-chloro-6-(trifluoromethyl)pyridin-4-yl]methanol (130 mg, 0.614 mmol, from Step A) and methyl iodide (42 μL, 0.68 mmol) in N,N-dimethylformamide (0.65 mL, 8.4 mmol) was added potassium carbonate (250 mg, 1.8 mmol). The mixture was sealed and stirred at room temperature for 24 hours. Additional methyl iodide (42 μL, 0.68 mmol) was added. The mixture was stirred again for 24 hours, then was diluted with water and extracted with EtOAc. The extract was washed with water (3×), followed by brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel, eluting with a gradient from 0-20% EtOAc in Hexanes, afforded product as a colorless oil (56 mg, 40%). 1H NMR (300 MHz, CDCl3) δ 7.56 (s, 1H), 7.50 (s, 1H), 4.53 (s, 2H), 3.48 (s, 3H); 19F NMR (282 MHz, CDCl3) δ−68.45 (s); LCMS (M+H)+: 226.1.

1. customThe mixture was sealed
2. stirringThe mixture was stirred again for 24 hours
3. extractionextracted with EtOAc
4. washThe extract was washed with water (3×)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. washFlash chromatography on silica gel, eluting with a gradient from 0-20% EtOAc in Hexanes

ORD record

ord-dff364983d38475182d7a1df728e9008

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933085B2