Water → 2,4-Difluoro-6-(2-hydroxyethyl)phenol

HRID 921168Notes

Reaction equation

HRID 921168 reaction equation
[F:1][C:2]1[C:3]([O:12]C)=[C:4]([CH2:9][CH2:10][OH:11])[CH:5]=[C:6]([F:8])[CH:7]=1.B(Br)(Br)Br.O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([CH2:9][CH2:10][OH:11])[C:3]=1[OH:12]

Participants

5

Reactant 3

HCID 962WaterHCID 25134Boron tribromideHCID 552683042-(3,5-Difluoro-2-methoxyphenyl)ethan-1-ol

Product 1

HCID 1172770622,4-Difluoro-6-(2-hydroxyethyl)phenolYield 57.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(3,5-difluoro-2-methoxyphenyl)ethanol (850 mg, 4.52 mmol) in DCM (30 mL) at 0° C. was added 1M BBr3 (13.55 mL, 13.55 mmol) solution. The resulting mixture was slowly warmed to room temp and stir for 3 h. water (dropwise) was then added and after the bubbling stops mixture was diluted with DCM and washed with water, dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (5-50%, EtOAc/hexane) to afford 2,4-difluoro-6-(2-hydroxyethyl)phenol (450 mg, 2.58 mmol, 57.2% yield) as clear viscous oil. 1H NMR (400 MHz, CDCl3) δ 7.14 (br. s., 1H), 6.80-6.73 (m, 1H), 6.66 (dt, J=8.8, 2.4 Hz, 1H), 4.01-3.95 (m, 2H), 2.93 (t, J=5.5 Hz, 2H), 2.32 (br. s., 1H).

Workup

  1. additionwas then added
  2. washwashed with water
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was then purified by Biotage (5-50%, EtOAc/hexane)

Sources & evidence

ORD record
ord-7c8436b74e484c3f98639f5165261a91
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

Loading…