Water → 5-[3-chloro-4-(propan-2-yloxy)phenyl]-1-methyl-1H-pyrazole-4-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-(3-chloro-4-isopropoxyphenyl)-1H-pyrazole-4-carbaldehyde (530 mg, 1.76 mmol, 1.00 equiv) and potassium carbonate (828 mg, 5.99 mmol, 3.40 equiv) in acetonitrile (100 mL) was added iodomethane (852 mg, 6.00 mmol, 3.41 equiv) dropwise. The reaction was stirred at 70° C. for 8 h. The resulting mixture was cooled to room temperature then concentrated under vacuum. The residue was dissolved in 20 mL of H2O and then extracted with 3×30 mL ethyl acetate. The combined organic layers was washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Prep-HPLC with the following conditions: Column, XSelect CSH Prep C18 OBD Column, 5 μm, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and MeCN (38.0% MeCN up to 45.0% in 15 min); Detector, UV 254/220 nm to afford 100 mg (18%) of 5-[3-chloro-4-(propan-2-yloxy)phenyl]-1-methyl-1H-pyrazole-4-carbaldehyde as colorless oil. 1H-NMR (300 MHz, DMSO-d6): δ 9.55 (s, 1H), 8.03 (s, 1H), 7.73 (d, J=2.1 Hz, 1H), 7.51 (dd, J=8.4 Hz, 2.1 Hz, 1H), 7.34 (d, J=8.4 Hz, 1H), 4.85-4.77 (m, 1H), 3.78 (s, 3H), 1.33 (d, J=7.5 Hz, 6H) ppm. LCMS (method C, ESI): RT=0.92 min, m/z=279.0 [M+H]+ and 120 mg (22%) of the other regioisomer, 3-(3-chloro-4-isopropoxyphenyl)-1-methyl-1H-pyrazole-4-carbaldehyde as a colorless oil. 1H-NMR (300 MHz, DMSO-d6): δ 9.83 (s, 1H), 8.51 (s, 1H), 7.96 (d, J=2.1 Hz, 1H), 7.82 (dd, J=8.4 Hz, 2.1 Hz, 1H), 7.23 (d, J=8.4 Hz, 1H), 4.77-4.69 (m, 1H), 3.94 (s, 3H), 1.32 (d, J=7.5 Hz, 6H) ppm.

Provenance & Evidence