Dichloromethane → 1-(4-Bromophenyl)-2,2,2-trifluoroethanol

To 4′-bromo-2,2,2-trifluoroacetophenone (5.0 g, 19.76 mmol) in THF (50 mls) at 0° C. was added NaBH4 (1.5 g, 39.52 mmol). The mixture was warmed to room temperature and stirred for 1 hour. The reaction was complete by TLC (CH2Cl2). The mixture was quenched with H2O, rotary evaporated to remove most of the THF, and extracted 2 times with CH2Cl2. The organics were combined, washed with brine, concentrated to a small volume and filtered through a plug of silica gel. The silica was washed with CH2Cl2 to elute the product, and the resulting solution was concentrated to give 4.65 g of 1-(4-bromophenyl)-2,2,2-trifluoroethanol. Yield: 92%. 1-(4-Bromophenyl)-2,2,2-trifluoroethanol (0.13 g, 0.525 mmol), m-tolylboronic acid (0.1 g, 0.736 mmol), Fibercat (4.28% Pd, 47 mgs, 0.0157 mmol Pd), K2CO3 (0.22 g, 1.576 mmol), EtOH (3 mls), and H2O (0.5 mls) were combined and heated at 80° C. for 4 hours. The reaction was shown complete by TLC (CH2Cl2). The mixture was cooled, filtered, concentrated, slurried in CH2Cl2, and chromatographed over silica gel (CH2Cl2) to give 0.1 g of 2,2,2-trifluoro-1-(3′-methylbiphenyl-2-yl)ethanol. Yield: 72%.

1. customThe mixture was quenched with H2O
2. customrotary evaporated
3. customto remove most of the THF
4. extractionextracted 2 times with CH2Cl2
5. washwashed with brine
6. concentrationconcentrated to a small volume
7. filtrationfiltered through a plug of silica gel
8. washThe silica was washed with CH2Cl2
9. washto elute the product
10. concentrationthe resulting solution was concentrated

ORD record

ord-2aeab4fdafad404598c8ba8124a1c2c7

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410121B2