Dimethyl Sulfoxide → 5-Methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carbaldehyde

Temperature

-78 °C

To a stirred solution of oxalyl chloride (1.69 mL, 19.4 mmol) in dichloromethane (10 mL) at −78° C. was added DMSO (3.45 mL, 18.6 mmol) as a solution in dichloromethane (5 mL) dropwise over a period of 10 min. To this reaction mixture was added [5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]methanol (Step 1, 4.2 g, 19.42 mmol) as a solution in dichloromethane (50 mL) dropwise over a period of 30 min. The mixture was stirred at −78° C. for 1.5 h. and triethylamine (13.5 mL, 97.1 mmol) in dichloromethane (5 mL) was then added dropwise. The resultant mixture was warmed to 0° C. and stirred for 20 min. To this mixture was added water (25 mL) dropwise, followed by dichloromethane (100 mL). The organic layer was separated, and the aqueous layer was extracted with dichloromethane (1×100 mL). The combined organic extracts were washed with HCl (0.5 M aq., 1×50 mL), dried (Na2SO4), and filtered. The organic layer was passed through a small plug of silica gel using ethyl acetate as eluent, and was concentrated under reduced pressure to afford the title compound as a yellow oil (3.7 g, 89%): 1H NMR (300 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.12 (d, 2H), 7.03 (d, 2H), 6.57 (s, 1H), 5.36 (s, 2H), 2.25 (s, 3H), 2.23 (s, 3H): ES-MS m/z 214.98, HPLC RT (Method A) 3.33 min.

1. stirringstirred for 20 min
2. customThe organic layer was separated
3. extractionthe aqueous layer was extracted with dichloromethane (1×100 mL)
4. washThe combined organic extracts were washed with HCl (0.5 M aq., 1×50 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationwas concentrated under reduced pressure

ORD record

ord-c2cc2de5beb3482c925ed78cbb163ec2

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796253B2