Benzonitrile, 2,6-difluoro-3-hydroxy- synthesis

Yield:946796-26-5 55%

Reaction Conditions:

Stage #1: 2,6-difluoro-3-methoxy-benzonitrilewith boron tribromide in dichloromethane at 20; for 120 h;
Stage #2: with water

Steps:

Synthesised from commercially available 2,6-difluoro-3-methoxybenzenecarbonitrile. Boron tribromide solution (1.0 M in CH₂Cl₂, 118.3 ml, 118.3 mmol, 2 equiv.) was added slowly, dropwise to stirred solution of 2,6-difluoro-3-methoxybenzenecarbonitrile (10 g, 59.1 mmol, 1 equiv.) in CH₂Cl₂ (270 ml), at room temperature The reaction mixture was stirred at room temperature for 5 days. The reaction mixture was poured into water (600 ml), separated and extracted with CH₂Cl₂ (200 ml×2). The extracts were washed with water (250 ml×3) and dried (Na₂SO₄) to give a buff solid (7.15 g). This was dissolved in dichloromethane (250 ml) and extracted with dilute aqueous NaOH (6 g in 250 ml of water×2). The basic extracts were washed with CH₂Cl₂ (100 ml×3) and then acidified to pH 2 using concentrated HCl, extracted with CH₂Cl₂ (150 ml×4), washed with water (100 ml×2) and dried (Na₂SO₄) to give the desired compound as a cream solid (5.05 g). Yield 55%, mp 119-121° C., HPLC (Gemini C18, 50×4.6 mm): m/z 154 [M-H]^-, Rt=3.07 min.

References:

US2010/298388,2010,A1 Location in patent:Page/Page column 7