Potassium Phosphate, Tribasic → 4-Chloro-2-cyclopropylbenzaldehyde

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).

1. temperaturethe mixture was heated
2. temperatureunder reflux, overnight
3. temperatureAfter cooling to rt
4. customthe layers were separated
5. washThe organic layer was washed with brine (20 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography (SiO2, DCM/hexanes 1:3)

ORD record

ord-912ba6cacb634541b1c015fc7b546a0e

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2