Tetrahydrofuran → 2,2-Difluoro-2-(4-fluoronaphthyl)acetic Acid

HRID 1060219Notes

Reaction equation

HRID 1060219 reaction equation
[F:1][C:2]([F:19])([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([F:18])=[CH:10][CH:9]=1)[C:3]([O:5]CC)=[O:4].C1COCC1.[OH-].[Na+]>CO.O>[F:19][C:2]([F:1])([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([F:18])=[CH:10][CH:9]=1)[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 22475360Ethyl 2,2-difluoro-2-(4-fluoronaphthyl)acetate

Product 1

HCID 224753182,2-Difluoro-2-(4-fluoronaphthyl)acetic AcidYield 94.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 2,2-difluoro-2-(4-fluoronaphthyl)acetate (9.6 g, 35.8 mmol), as prepared in the preceding step, in methanol (20 mL) and THF (20 mL) was added a solution of NaOH (2.0 g, 50 mmol) in water (40 mL). The reaction mixture was stirred at room temperature for 2 hours. After evaporating the methanol and THF in vacuo, the aqueous phase was acidified to pH 2 using 10% HCl, and extracted with DCM (3×50 mL). The extracts were combined, washed with brine, dried over Na2SO4, and concentrated to give the title compound (8.1 g, 94% yield) as an off white solid. 1H-NMR (400 MHz, CDCl3) δ 9.68 (br s, 1H), 8.18 (m, 2H), 7.83 (dd, J=8.1, 5.3 Hz, 1H), 7.62 (m, 2H), 7.19 (t,J=8.3 Hz, 1H).

Workup

  1. customAfter evaporating the methanol and THF in vacuo
  2. extractionextracted with DCM (3×50 mL)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e3a2836b061a4a17b4ee4f8821ef123a
Source dataset
uspto-grants-2003_02
Patent number
US06521663B2

Reaction notes

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