1-Bromo-3,5-dimethoxybenzene → (3,4-Bis-difluoromethoxy-phenyl)-(3,5-dimethoxy-phenyl)-methanol

n-Butyl lithium (2.5 M, 3.7 mL) was added to s stirred solution of 3,5-dimethoxy-bromobenzene (2.0 g, 9.2 mmol) in THF (15 mL) at −65° C. After stirring for 30 min, a solution of 3,4-bis-difluoromethoxy-benzaldehyde (2.0 g, 8.4 mmol) in THF (15 mL) was added slowly. The resulting mixture was stirred at −65° C. for 6 h and then quenched with isopropanol (5 mL). Water (40 mL) was added and the mixture was extracted with ether (3×60 mL). The combined organic layers were washed with water (2×40 mL), brine (40 mL), and dried (MgSO4). Solvent was removed and the residue was purified by flash chromatography (Silica gel, Hexane:EtOAc 7:3) to afford (3,4-bis-difluoromethoxy-phenyl)-(3,5-dimethoxy-phenyl)-methanol (1.3 g, 42%): 1H NMR (CDCl3) δ 7.32 (m, 1H), 7.19 (m, 2H), 6.86-6.19 (m 5H), 5.69 (d, J=2 Hz, 1H), 3.76 (s, 6H), 2.47 (d, J=2 Hz, 1H).

1. stirringThe resulting mixture was stirred at −65° C. for 6 h
2. customquenched with isopropanol (5 mL)
3. additionWater (40 mL) was added
4. extractionthe mixture was extracted with ether (3×60 mL)
5. washThe combined organic layers were washed with water (2×40 mL), brine (40 mL)
6. dry with materialdried (MgSO4)
7. customSolvent was removed
8. customthe residue was purified by flash chromatography (Silica gel, Hexane:EtOAc 7:3)

ORD record

ord-6877b8658da24057b291ebedefd14572

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07312241B2