3-Hydroxybenzyl alcohol → (3-(5-Methylpyridin-2-yloxy)phenyl)methanol

HRID 1666402Notes

Reaction equation

HRID 1666402 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.F[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[CH3:17][C:14]1[CH:15]=[CH:16][C:11]([O:9][C:5]2[CH:4]=[C:3]([CH2:2][OH:1])[CH:8]=[CH:7][CH:6]=2)=[N:12][CH:13]=1

Participants

5

Reactant 3

HCID 1023-Hydroxybenzyl alcoholHCID 10796Cesium carbonateHCID 27746352-Fluoro-5-methylpyridine

Product 1

HCID 66875995(3-(5-Methylpyridin-2-yloxy)phenyl)methanolYield 53%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

3-Hydroxymethyl-phenol (5.04 g, 40.6 mmol), 2-fluoro-5-methyl-pyridine (4.1 g, 37 mmol,) and cesium carbonate (15.0 g, 46.1 mmol) were suspended in dimethylsulfoxide (50 mL) and heated to 110° C. After stirring for 16 h, the reaction was partitioned between water (500 mL) and ethyl acetate (500 mL). The organic layer was separated and the aqueous was extracted again with ethyl acetate. The combined organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (10-20%, EtOAc:heptane) to afford the title compound (4.2 g, 53% yield) as a thick oil.

Workup

  1. customthe reaction was partitioned between water (500 mL) and ethyl acetate (500 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous was extracted again with ethyl acetate
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (10-20%, EtOAc:heptane)

Sources & evidence

ORD record
ord-7217f428e1cc4a919b4c4b91c9eac15b
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…