Water → {5-Fluoro-2-(methyloxy)-3-[(phenylmethyl)oxy]phenyl}methanol

HRID 253280Notes

Reaction equation

HRID 253280 reaction equation
IC.[C:3](=O)([O-])[O-].[Cs+].[Cs+].[F:9][C:10]1[CH:15]=[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:13]([OH:24])=[C:12]([CH2:25][OH:26])[CH:11]=1.O>CN(C=O)C>[F:9][C:10]1[CH:15]=[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:13]([O:24][CH3:3])=[C:12]([CH2:25][OH:26])[CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 668904684-Fluoro-2-(hydroxymethyl)-6-[(phenylmethyl)oxy]phenol

Product 1

HCID 66890315{5-Fluoro-2-(methyloxy)-3-[(phenylmethyl)oxy]phenyl}methanolYield 79.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Iodomethane (24 mL, 382 mmol) and cesium carbonate (25 g, 76.4 mmol) were added to a solution of 4-fluoro-2-(hydroxymethyl)-6-[(phenylmethyl)oxy]phenol (9.5 g, 38.2 mmol) in DMF (125 mL). The mixture was stirred for 1 h at rt, and then water was added. The resulting aqueous mixture was extracted twice with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide {5-fluoro-2-(methyloxy)-3-[(phenylmethyl)oxy]phenyl}methanol as a yellow solid (7.9 g, 30.2 mmol, 79% yield). 1H NMR (400 MHz, CDCl3): δ 7.44-7.32 (m, 5H), 6.69-6.63 (m, 2H), 5.08 (s, 2H), 4.67 (d, 2H), 3.86 (s, 3H).

Workup

  1. extractionThe resulting aqueous mixture was extracted twice with ethyl acetate
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

Sources & evidence

ORD record
ord-25bf6cd0e3f348928455b85384b95e2c
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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