Diisopropylamine → (4,6-dichloropyrimidin-5-yl)[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (2.5 M in hexanes, 240 mL, 0.60 mol) was added drop-wise to a solution of diisopropylamine (85.2 mL, 0.60 mol) in tetrahydrofuran (600 mL) at −78° C. After the reaction had stirred for 30 minutes at −78° C., a solution of 4,6-dichloropyrimidine (89.4 g, 0.600 mol) in tetrahydrofuran (600 mL) was added drop-wise at about −90° C., and stirring was continued for 1 hour. To this mixture was added drop-wise a solution of 5-(4-methylphenyl)-1-methyl-1H-pyrazole-4-carbaldehyde (C3) (60.0 g, 300 mmol) in tetrahydrofuran (600 mL) at about −90° C. After completion of the addition, the reaction mixture was stirred at this temperature for 2 hours. The reaction mixture was quenched with acetic acid (60 g); the mixture was warmed to room temperature, and then concentrated under reduced pressure to remove tetrahydrofuran. The residue was dissolved in ethyl acetate (2 L) and washed with saturated aqueous sodium bicarbonate solution (1 L). The organic layer was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, and concentrated in vacuo. Recrystallization from ethyl acetate yielded the product as a white solid. Yield: 82.0 g, 235 mmol, 78%. 1H NMR (400 MHz, CDCl3) δ 2.39 (s, 3H), 3.72 (s, 3H), 6.26 (s, 1H), 7.17 (br AB quartet, JAB=8 Hz, ΔνAB=32 Hz, 4H), 7.66 (s, 1H), 8.55 (s, 1H).

Provenance & Evidence