HCID 68291719, compound → 3-Fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid

HRID 72958Notes

Reaction equation

HRID 72958 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]([OH:21])([CH3:20])[CH3:19])[C:5]([O:7]CC1C=CC=CC=1)=[O:6].[H][H]>CO.[Pd]>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]([OH:21])([CH3:19])[CH3:20])[C:5]([OH:7])=[O:6]

Participants

5

Reactant 2

HCID 68291719HCID 68291719, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 682908483-Fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acidYield 96%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid (9.1 g, 45.7 mmol) in DMF (40 mL) was added cesium carbonate (22.3 g, 68.5 mmol) followed by benzyl bromide (11.7 g, 8.1 mL, 68.5 mmol) and reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed sequentially with H2O (3×10 mL), brine solution. The organics were separated and dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography eluting with 10-20% EtOAc-hexanes to provide benzyl 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoate (2.8 g, 21%) ESI-MS m/z calc. 288.2. Found 289.3 (M+1)+; Retention time: 1.79 min (3 min run). To a solution of benzyl 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoate (2.8 g, 9.71 mmol) in MeOH (50 mL) was added palladium on carbon (100 mg, 0.09 mmol) and the reaction mixture was subjected to an atmosphere of hydrogen for 16 hours. The catalyst was removed via filtration over Celite® and the solvent removed in vacuo to provide 3-fluoro-4-(1-hydroxy-1-methyl-ethyl)benzoic acid (1.8 g, 96%) as a white solid. ESI-MS m/z calc. 198.2. Found 199.9 (M+1)+; Retention time: 0.91 minutes (3 min run).

Workup

  1. customRetention time: 1.79 min (3 min run)
  2. customThe catalyst was removed via filtration over Celite®
  3. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-718ee2b52d9e40daa045fb83ffc61b52
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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