Tetrahydrofuran → 2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

4-Bromo-2-chlorobenzonitrile (30 g, 139 mmol), 90 ml of THF and 360 ml of toluene were placed in reaction vessel under nitrogen atmosphere. Bis(triphenylphosphine)-palladium(II) chloride (4.57 g, 6.51 mmol), Na2CO3 (33.1 g, 312 mmol), 180 ml of water and tetrabutylammonium bromide (0.894 g, 2.77 mmol) were added. The reaction mixture was heated up to 42° C. 1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester (42.4 g; 152 mmol) was added in three portions within one hour. The reaction was agitated at 42° C. for one hour followed with addition of 180 ml of water and cool down. The reaction mixture was filtered and layers separated. Organic phase was washed with 400 ml of water. The layers were separated and the toluene phase was distilled close to dryness. 180 ml of ethanol was added to the warm residue and the mixture was cooled down to 5° C. for three hours. The precipitate was filtered and washed with cold ethanol. 36.4 g of the title compound was obtained after vacuum drying. 1H-NMR (400 MHz, DMSO-d6): δ 1.48-1.70 (m, 3H), 1.78-1.86 (m, 1H), 1.90-2.00 (m, 1H), 2.29-2.46 (m, 1H), 3.55-3.68 (m, 1H), 3.93-4.04 (m, 1H), 5.29 (dd, 1H), 6.72 (d, 1H), 7.65 (d, 1H), 7.72 (dd, 1H), 7.92 (d, 1H), 8.13 (d, 1H).

Provenance & Evidence