Methyl iodide → HCID 57527163, compound

To a solution of 3-(2-fluorophenyl)-1H-pyrazole (8.62 g, 53.2 mmol, 1.0 eq.) in methanol (133 mL) under nitrogen at 0° C. were added iodomethane (4.3 mL, 68.9 mmol, 1.3 eq.), NaOH (aq., 6 N, 34 mL, 204.0 mmol, 3.8 eq.) and nBu4NBr (0.68 g, 2.11 mmol, 0.04 eq.). The cold bath was then removed, and the reaction mixture was stirred to room temperature. After 6.5 h, iodomethane was added (4 mL), and the reaction mixture was stirred overnight. More iodomethane (4 mL) and NaOH (aq., 6 N, 20 mL) were added, and the reaction mixture was stirred overnight. It was then concentrated in vacuo not to dryness, diluted with EtOAc, and the two layers were separated. The aqueous layer was extracted with EtOAc, and the organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo. Silica gel chromatography using hexanes:EtOAc (15:2) as eluent afforded a mixture of 3-(2-fluorophenyl)-1-methyl-1H-pyrazole and 5-(2-fluorophenyl)-1-methyl-1H-pyrazole (6.78 g, 72% yield).

1. customThe cold bath was then removed
2. additioniodomethane was added (4 mL)
3. stirringthe reaction mixture was stirred overnight
4. additionMore iodomethane (4 mL) and NaOH (aq., 6 N, 20 mL) were added
5. stirringthe reaction mixture was stirred overnight
6. concentrationIt was then concentrated in vacuo not to dryness
7. additiondiluted with EtOAc
8. customthe two layers were separated
9. extractionThe aqueous layer was extracted with EtOAc
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customafforded

ORD record

ord-86f54ebb74504ff6867b33226fc5ab27

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07473784B2