Iodine → (4-Bromo-3-fluorophenyl)methanol

A suspension of 4-bromo-3-fluorobenzoic acid (84) (1.61 g, 7.35 mmol) in anhydrous THF (10 mL, then 4×3 mL to rinse) under N2 was added drop-wise (over 40 min) to a suspension of sodium borohydride (400 mg, 10.6 mmol) in anhydrous THF (15 mL) under N2, and then the mixture was cooled in an ice bath. A solution of iodine (1.008 g, 3.97 mmol) in anhydrous THF (10 mL, then 2×3 mL) was added drop-wise (over 35 min) to the stirred solution and then the mixture was stirred at room temperature for 14 h. The mixture was concentrated under reduced pressure and then treated successively with water (20 mL), 10% HCl (3.4 mL) and water (20 mL), and extracted with CH2Cl2 (4×50 mL). The extracts were evaporated to dryness and the residue was chromatographed on silica gel, eluting with 50% CH2Cl2/petroleum ether, to give (4-bromo-3-fluorophenyl)methanol (85) (1.096 g, 73%) as a white solid: mp (CH2Cl2/petroleum ether) 39-40° C.; 1H NMR (CDCl3) δ 7.52 (dd, J=8.0, 7.2 Hz, 1H), 7.16 (dd, J=9.3, 1.8 Hz, 1H), 7.02 (dd, J=8.2, 1.8 Hz, 1H), 4.67 (d, J=5.9 Hz, 2H), 1.75 (t, J=5.9 Hz, 1H); HREIMS calcd for C7H6BrFO m/z (M+) 205.9567, 203.9586, found 205.9566, 203.9580.

1. wash4×3 mL to rinse) under N2
2. additionwas added drop-wise (over 40 min)
3. temperaturethe mixture was cooled in an ice bath
4. concentrationThe mixture was concentrated under reduced pressure
5. additiontreated successively with water (20 mL), 10% HCl (3.4 mL) and water (20 mL)
6. extractionextracted with CH2Cl2 (4×50 mL)
7. customThe extracts were evaporated to dryness
8. customthe residue was chromatographed on silica gel
9. washeluting with 50% CH2Cl2/petroleum ether

ORD record

ord-81c0d2367e934a97b614d0e128b0b64e

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09198913B2