Benzyl Bromide → 3-(Benzyloxy)-2,2-difluoropropan-1-OL

HRID 2279884

Reaction equation

HRID 2279884 reaction equation
[F:1][C:2]([F:7])([CH2:5][OH:6])[CH2:3][OH:4].FC1C=CC(B(O)O)=CC=1.C([O-])([O-])=O.[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:24]([O:4][CH2:3][C:2]([F:7])([F:1])[CH2:5][OH:6])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 957442,2-Difluoropropane-1,3-diol2×HCID 2856454-Fluorophenylboronic acid

Product 1

HCID 584638693-(Benzyloxy)-2,2-difluoropropan-1-OLYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 2,2-difluoropropane-1,3-diol (Compound 59I, 6.0 g, 53.5 mmol), 4-fluorophenylboronic acid (1.5 g, 10.7 mmol) and K2CO3 (11.0 g, 80.3 mmol) in DMF (50 mL) was treated with benzyl bromide (8.9 mL, 74.9 mmol). The reaction mixture was stirred at RT for 72 h, diluted with ethyl acetate (200 mL) and washed with water (5×100 mL). The organic layer was dried over Na2SO4, filtered and concentrated to give yellow oil which was purified by column chromatography (SiO2, 20% ethyl acetate/hexanes) to give 5 g (50%) of the desired product as an oil. 1H NMR (500 MHz, CDCl3) δ 7.38-7.34 (m, 5H), 4.70 (s, 2H), 3.89-3.88 (m, 2H), 3.77 (t, J=12.6 Hz, 2H).

Workup

  1. washwashed with water (5×100 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give yellow oil which
  6. customwas purified by column chromatography (SiO2, 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f744759d3a4745b4a3e913426fd41e1d
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Linked notes

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