4-Hydroxybenzyl Alcohol → 1-[4-(Hydroxymethyl)phenoxy]propan-2-one

HRID 1479251Notes

Reaction equation

HRID 1479251 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:17][C:18](=[O:20])[CH3:19]>CC(C)=O>[OH:7][CH2:6][C:5]1[CH:8]=[CH:9][C:2]([O:1][CH2:17][C:18](=[O:20])[CH3:19])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 1254-Hydroxybenzyl AlcoholHCID 6571ChloroacetoneHCID 11430Potassium Carbonate

Product 1

HCID 177562771-[4-(Hydroxymethyl)phenoxy]propan-2-oneYield 98%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of 4-hydroxybenzyl alcohol (1.0 g, 8.06 mmol) in acetone (80 mL) was added potassium carbonate (1.34 g, 9.68 mmol) and chloroacetone (0.771 mL, 9.68 mmol). After completion of addition the reaction mixture was heated to reflux. After 20 hours the reaction mixture was cooled down to room temperature and the solvent was removed. Water and ethyl acetate were added to the crude material. The aqueous layer was separated and extracted with ethyl acetate (3×, 100 mL). All combined organic layers were dried over Na2SO4, filtered, and concentrated to provide an oil. The crude material was purified using silica gel chromatography (gradient from 4:1 to 1:1 pentane:ethyl acetate) to provide the desired product (0.981 g, 5.45 mmol) in 98% yield. 1H (CDCl3, 600 MHz): δ 7.30 (2H, d, J=8.7 Hz), 6.87 (2H, d, J=8.7 Hz), 4.63 (2H, d, J=5.7 Hz), 4.54 (2H, s), 2.27 (3H, s), 1.66 (1H, t, J=5.8 Hz); 13C (CDCl3, 150 MHz): δ 205.7, 157.3, 134.3, 128.8, 114.6, 73.1, 64.8, 26.6.

Workup

  1. additionAfter completion of addition the reaction mixture
  2. temperaturewas heated to reflux
  3. customthe solvent was removed
  4. additionWater and ethyl acetate were added to the crude material
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate (3×, 100 mL)
  7. dry with materialAll combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto provide an oil
  11. customThe crude material was purified

Sources & evidence

ORD record
ord-375e4017a2eb4a3c81e18507b585fe47
Source dataset
uspto-grants-2016_08
Patent number
US09408927B2

Reaction notes

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