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

HRID 78881Notes

Reaction equation

HRID 78881 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-f33efe4f142a439b81d76e8bc3404b21
Source dataset
uspto-grants-2014_09
Patent number
US08841477B2

Reaction notes

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