Methyl iodide → 1H-Pyrazole-4-carboxylic acid, 1-methyl-3-(trifluoromethyl)-, ethyl ester

HRID 220451Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:7]([C:11]([F:14])([F:13])[F:12])=[N:8][NH:9][CH:10]=1)=[O:5])[CH3:2].[H-].[Na+].I[CH3:18]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([C:11]([F:13])([F:14])[F:12])=[N:8][N:9]([CH3:18])[CH:10]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

Dissolve 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (2.0 g, 9.61 mmol) in N,N-dimethylformamide (20 mL) and cool to 0° C. Add sodium hydride (0.58 g, 14.42 mmol, 60% dispersion in oil) and stir at 0° C. for 20 min. Add iodomethane (0.90 mL, 14.42 mmol) and allow to warm to room temperature over 18 hr. Partition between ethyl acetate (100 mL) and water (50 mL). Separate the organic layer and wash with water (5×50 mL) and saturated aqueous sodium chloride solution (50 mL). Dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 90:10 hexanes:ethyl acetate), to give 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.74 g, 81.7%). 1H-NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 4.27 (q, 2H), 3.95 (s, 3H), 1.33 (t, 3H).

Workup

temperatureto warm to room temperature over 18 hr
customPartition between ethyl acetate (100 mL) and water (50 mL)
customSeparate the organic layer
washwash with water (5×50 mL) and saturated aqueous sodium chloride solution (50 mL)
dry with materialDry (sodium sulfate)
filtrationfilter
concentrationconcentrate
custompurify
wash(silica gel chromatography, eluting with 90:10 hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-19935b4438d54a90887ff387e1d46a64
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202873B2

Reaction notes

Loading…