3-Hydroxybenzyl alcohol → (3-((5-(Trifluoromethyl)pyridin-2-yl)oxy)phenyl)methanol

HRID 1666316Notes

Reaction equation

HRID 1666316 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.Cl[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][N:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:18][C:17]([F:20])([F:19])[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 11430Potassium CarbonateHCID 923422-Chloro-5-(trifluoromethyl)pyridine

Product 1

HCID 66875457(3-((5-(Trifluoromethyl)pyridin-2-yl)oxy)phenyl)methanolYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

3-Hydroxymethyl-phenol (5.00 g, 40.3 mmol, from Lancaster Synthesis), 2-chloro-5-trifluoromethyl-pyridine (7.31 g, 40.3 mmol, from TCI America) and potassium carbonate (6.96 g, 50.3 mmol) were suspended in dimethylformamide (80 mL) and heated to 95° C. After stirring for 16 h, the solvent was distilled off in vacuo at 65° C., and a residue was partitioned between water and heptane/ethyl acetate (1:1). The organic layer was separated and the aqueous was extracted again with heptane/ethyl acetate (1:1). The combined organic layer was dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by silica gel chromatography (10-60%, EtOAc:heptane) to afford the desired product (5.70 g, 53% yield) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.73 (s, 2H) 7.02 (dt, J=8.66, 0.57 Hz, 1H) 7.04-7.11 (m, J=8.06, 2.40, 0.50, 0.50 Hz, 1H) 7.15-7.19 (m, 1H) 7.25 (ddd, J=8.39, 1.60, 0.80 Hz, 1H) 7.42 (t, J=7.87 Hz, 1H) 7.90 (ddd, J=8.67, 2.55, 0.50 Hz, 1H) 8.43 (td, J=1.68, 0.84 Hz, 1H).

Workup

  1. distillationthe solvent was distilled off in vacuo at 65° C.
  2. customa residue was partitioned between water and heptane/ethyl acetate (1:1)
  3. customThe organic layer was separated
  4. extractionthe aqueous was extracted again with heptane/ethyl acetate (1:1)
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a residue
  9. customThe residue was purified by silica gel chromatography (10-60%, EtOAc:heptane)

Sources & evidence

ORD record
ord-7cc751717ec946718fef007f5f6c8b0a
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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