Phenol → HCID 22351358, compound

HRID 896884Notes

Reaction equation

HRID 896884 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[C:4](F)[CH:3]=1.[C:19]1([OH:25])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[C:4]([O:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 22351348Benzyl 4-bromo-2-fluorobenzoate

Product 1

HCID 22351358HCID 22351358, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Phenylmethyl 4-bromo-2-fluorobenzoate (Example 189, 260 mg, 0.84 mmol) was combined with phenol (160 mg, 1.68 mmol, 2.0 eq.) and solid potassium carbonate (580 mg, 4.21 mmol, 5.0 eq.) in anhydrous N,N-dimethylformamide and was heated at 85° C. for 5 hours. The mixture was cooled and partitioned between diethyl ether and water. The aqueous layer was separated and extracted with fresh ether. The organic layers were combined, washed with brine (4×), dried (MgSO4), and concentrated in vacuo to a crude oil. The crude was purified by flash chromatography on silica gel eluted with 95:5 hexanes/ether to provide the title compound as a colorless oil that crystallized upon standing (110 mg, 34%): 1H NMR (300 MHz, CDCl3) δ 7.84 (d, 1 H), 7.39-7.27 (m, 7 H), 7.17-7.10 (m, 1 H), 6.98-6.91 (m, 2 H), 6.85 (d, 2 H), 5.30 (s, 2 H); Rf 0.51 (4:1 hexanes/diethyl ether).

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between diethyl ether and water
  3. customThe aqueous layer was separated
  4. extractionextracted with fresh ether
  5. washwashed with brine (4×)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo to a crude oil
  8. customThe crude was purified by flash chromatography on silica gel
  9. washeluted with 95:5 hexanes/ether

Sources & evidence

ORD record
ord-81a5c0b9a56d454aaaf171839fdec053
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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