Benzyl Bromide → (4-Benzyloxy-phenyl)-2-fluorophenyl-methanone

HRID 2174428Notes

Reaction equation

HRID 2174428 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)=[O:9].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>C(#N)C.O>[CH2:17]([O:16][C:13]1[CH:12]=[CH:11][C:10]([C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[O:9])=[CH:15][CH:14]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27832352-Fluoro-4'-hydroxybenzophenone

Product 1

HCID 57701069(4-Benzyloxy-phenyl)-2-fluorophenyl-methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

(2-Fluorophenyl)(4-hydroxyphenyl)methanone (9.0 g, 41.6 mmol), benzyl bromide (7.1 g, 41.6 mmol), and potassium carbonate (5.8 g, 41.6 mmol) were mixed in acetonitrile (60 mL). The resulting mixture was shaken at 70° C. overnight (15 h). After cooling to ambient temperature, EtOAc (200 mL) and water (100 mL) were added. The phases were separated, and the aqueous phase was further extracted with EtOAc (200 mL). The combined organic phase was washed with Na2CO3 (3×100 mL, saturated aqueous solution) and brine (100 mL), dried over Na2SO4 and filtered. Evaporation of the solvent under reduced pressure yielded 12.1 g, 95% as a slightly yellow solid. 1H-NMR (CDCl3) δ; 7.83 (dd, 2H, J=8.8 Hz and 1.2 Hz), 7.54-7.46 (m, 2H), 7.46-7.32 (m, 5H), 7.25 (m, 1H), 7.15 (m, 1H), 7.02 (d, 2H, J=9.0 Hz), 5.14 (s, 2H); 13C-NMR (CDCl3) δ 191.9, 163.1, 159.7 (d, J=251 Hz), 136.1, 132.5 (d, J=8.1 Hz), 132.3 (d, 2C, J=0.8 Hz), 130.4 (d, J=3.1 Hz), 130.4, 128.7 (2C), 128.3 (2C), 127.5, 127.5 (d, J=16.8 Hz), 124.2 (d, J=3.8 Hz), 116.1 (d, J=21.9 Hz), 114.6 (2C), 70.2.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customThe phases were separated
  3. extractionthe aqueous phase was further extracted with EtOAc (200 mL)
  4. washThe combined organic phase was washed with Na2CO3 (3×100 mL, saturated aqueous solution) and brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customEvaporation of the solvent under reduced pressure
  8. customyielded 12.1 g, 95% as a slightly yellow solid

Sources & evidence

ORD record
ord-42a531d443734496bcdb703ff2fb0d20
Source dataset
uspto-grants-2015_06
Patent number
US09061981B2

Reaction notes

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