2,6-difluoro-3-methoxybenzonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,6-difluoro-3-methoxybenzonitrile (4.42 g, 26.1 mmol) was dissolved in DCM (10 mL) at 0° C. then 1 M BBr3 (52.2 mL, 52.2 mmol) was added. The reaction mixture was then warmed up to RT and stirred overnight. The reaction mixture was poured into ice water and extracted with more DCM. The organic layer was separated, dried over Na2SO4, filtered, and evaporated to dryness to yield 2,6-difluoro-3-hydroxybenzonitrile: LC-MS: M+1=156. extracted with more DCM The organic layer was separated dried over Na2SO4 filtered evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2,6-difluoro-3-methoxybenzonitrile (0.30 g, 1.70 mmol) in EtOH (10 ml) was added hydroxylamine hydrochloride (0.12 g, 1.70 mmol) and NaOH (0.071 g, 1.70 mmol). The resulting reaction mixture was refluxed for 15 h. After the completion of the reaction (TLC monitoring), the mixture was concentrated, added EtOH and filtered. The filtrate was evaporated in vacuo and the crude residue was purified over silica gel (60-120 M, 30% EtOAc-Hexane) to get the desired product (0.15 g, 42%) as a white solid. The resulting reaction mixture was refluxed for 15 h After the completion of the reaction (TLC monitoring) the mixture was concentrated added EtOH filtered The filtrate was evaporated in vacuo the crude residue was purified over silica gel (60-120 M, 30% EtOAc-Hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice cold solution of DMF (0.45 ml) and acetonitrile (10 ml) was added oxalyl chloride (0.41 g, 0.28 ml, 3.20 mmol) dropwise while maintaining the temperature to 0° C. The reaction mixture was stirred at 0° C. for 40 min followed by addition of a solution of 2,6-difluoro-3-methoxybenzamide (0.50 g, 2.70 mmol) in DMF (4.5 ml).The resulting reaction mixture was stirred at 0° C. 40 min and then allowed to come to room temperature. After completion of reaction (10 min, TLC monitoring), triethyl amine (0.57 g, 0.80 ml, 5.67 mmol) was added dropwise. The reaction mass was concentrated in vacuo followed by addition of water (100 ml) and extraction with ethyl acetate (3×100 ml). The combined organics was washed with water, brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified over silica gel (60-120 M, 10% EtOAc-Hexane) to get the desired product (0.30 g, 66%) as a white solid. resulting reaction mixture was stirred at 0° C 40 min to come to room temperature was added dropwise The reaction mass was concentrated in vacuo followed by addition of water (100 ml) and extraction with ethyl acetate (3×100 ml) The combined organics was washed with water, brine dried (Na2SO4) filtered concentrated The crude residue was purified over silica gel (60-120 M, 10% EtOAc-Hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. separated extracted with CH2Cl2 (200 ml×2) The extracts were washed with water (250 ml×3) dried (Na2SO4)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,6-difluoro-3-methoxybenzonitrile (4.42 g, 26.1 mmol) was dissolved in DCM (10 mL) at 0° C. then 1 M BBr3 (52.2 mL, 52.2 mmol) was added. The reaction mixture was then warmed up to RT and stirred overnight. The reaction mixture was poured into ice water and extracted with more DCM. The organic layer was separated, dried over Na2SO4, filtered, and evaporated to dryness to yield 2,6-difluoro-3-hydroxybenzonitrile: LC-MS: M+1=156. extracted with more DCM The organic layer was separated dried over Na2SO4 filtered evaporated to dryness