4-chloro-2-cyclopropylbenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed mixture of toluene (60 mL) and water (9 mL) was added potassium cyclopropyl-trifluoroborate (0.91 g, 6.2 mmol) and tribasic potassium phosphate (6.37 g, 30 mmol). The resulting mixture was stirred for 15 min at rt, thereafter, 2-bromo-4-chlorobenzaldehyde (1.50 g, 6.84 mmol, WO2006044454), palladium(II) acetate (0.11 g, 0.5 mmol) and 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (0.48 g, 1.0 mmol) were added and the mixture was heated under reflux, overnight. After cooling to rt, water (50 mL) and ethyl acetate (50 mL) were added and the layers were separated. The organic layer was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, DCM/hexanes 1:3) to give 4-chloro-2-cyclopropyl-benzaldehyde (0.48 g, 2.6 mmol, 39%) as a colorless semi solid: 1H-NMR (CDCl3, Bruker 400 MHz) δ 0.80 (2 H, m), 1.08-1.17 (2 H, m), 2.58 (1 H, m), 7.10 (1 H, d, J=2 Hz), 7.29 (1 H, dd, J=8 Hz, 2 Hz), 7.75 (1 H, d, J=8 Hz), 10.6 (1 H, s). the mixture was heated under reflux, overnight After cooling to rt the layers were separated The organic layer was washed with brine (20 mL) dried (MgSO4) filtered concentrated in vacuo The residue was purified by column chromatography (SiO2, DCM/hexanes 1:3)