Benzyl Alcohol → 1-(Benzyloxy)-3-bromo-5-fluorobenzene

HRID 2236342Notes

Reaction equation

HRID 2236342 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[C:16](F)[CH:15]=[C:14]([F:19])[CH:13]=1>CC(N(C)C)=O>[CH2:1]([O:8][C:16]1[CH:15]=[C:14]([F:19])[CH:13]=[C:12]([Br:11])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 1363131-Bromo-3,5-difluorobenzene

Product 1

HCID 112545161-(Benzyloxy)-3-bromo-5-fluorobenzeneYield 74.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of benzyl alcohol (3.86 g, 20 mmol) in DMA (30 ml), NaH(60% dispersion in oil, 0.80 g, 20 mmol) was drop wisely added. After one hour, 1-bromo-3,5-difluorobenzen (3.86 g, 20 mmol) was added at such a rate to maintain the temperature no more than 40° C. The mixture was stirred at ambient temperature overnight. The reaction was quenched by water and extracted with EtOAc. It was purified via flash chromatography and gave the product (4.17 g, 74%) as colorless oil. Data are: 1H NMR (CDCl3, 300 MHz) δ 7.41-7.43 (m, 5H), 6.94 (m, 1H), 6.86 (dt, 1H), 6.63 (dt, 1H), 5.02 (s, 2H); 13C NMR (CDCl3, 75 MHz) δ 165.20, 161.89, 160.72, 160.56, 136.01, 128.94, 128.57, 127.77, 127.73, 122.99, 122.83, 114.58, 114.53, 112.18, 111.84, 102.29, 101.96, 70.76; 19F NMR (CDCl3, 282 MHz) δ-31129.40 (t, J=2583.12 Hz).

Workup

  1. additionwisely added
  2. temperatureto maintain the temperature no more than 40° C
  3. customThe reaction was quenched by water
  4. extractionextracted with EtOAc
  5. customIt was purified via flash chromatography

Sources & evidence

ORD record
ord-f354e08fd1394c03a89fdae7deccff67
Source dataset
uspto-grants-2010_05
Patent number
US07714161B2

Reaction notes

Loading…