5-fluoro-2-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(5-Fluoro-2-methoxyphenoxy)acetaldehyde diethylacetal A suspension of 10.8 g of 5-fluoro-2-methoxyphenol and 12.6 g of potassium carbonate in 45 ml of N,N-dimethylformamide was heated for 45 minutes at 100° C. To the reaction mixture were added 18.5 ml of chloroacetaldehyde diethylacetal and 12.7 g of potassium iodide and the reaction mixture was heated for 4 hours at 140° C. After cooling, the reaction mixture was poured into ice water and extracted with ether. The extract was washed with aqueous sodium hydroxide solution and water, dried and evaporated. The residue was chromatographed on silica gel using chloroform as an eluant to give 11.8 g of the desired compound as a colorless oil. the reaction mixture was heated for 4 hours at 140° C After cooling extracted with ether The extract was washed with aqueous sodium hydroxide solution and water dried evaporated The residue was chromatographed on silica gel

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(5-Fluoro-2-methoxyphenoxy)acetaldehyde diethylacetal A suspension of 10.8 g of 5-fluoro-2-methoxyphenol and 12.6 g of potassium carbonate in 45 ml of N,N-dimethylformamide was heated for 45 minutes at 100° C. To the reaction mixture were added 18.5 ml of chloroacetaldehyde diethylacetal and 12.7 g of potassium iodide and the reaction mixture was heated for 4 hours at 140° C. After cooling, the reaction mixture was poured into ice water and extracted with ether. The extract was washed with aqueous sodium hydroxide solution and water, dried and evaporated. The residue was chromatographed on silica gel using chloroform as an eluant to give 11.8 g of the desired compound as a colorless oil. the reaction mixture was heated for 4 hours at 140° C After cooling extracted with ether The extract was washed with aqueous sodium hydroxide solution and water dried evaporated The residue was chromatographed on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 8.75 g of 5-fluoro-2-methoxyphenol, 10.9 g of ethylene carbonate and 8.50 g of potassium carbonate in 12 ml of toluene was refluxed for 2.5 hours. The reaction mixture was diluted with benzene, washed with water, dried and evaporated. The residue was distilled to give 9.15 g of 2-(5-fluoro-2-methoxyphenoxy)ethanol as colorless oil, b.p. 138°-140° C. (8mmHg). was refluxed for 2.5 hours washed with water dried evaporated The residue was distilled

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 10.0 g of 5-fluoro-2-methoxyphenol, 52.9 g of ethylenebromide and 14.6 g of potassium carbonate in 50 ml of N,N-dimethylformamide was heated for 11 hours at 80° C. After cooling, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, dried and evaporated. The residue was chromatographed on silica gel using 50% chloroform-n-hexane as an eluent to give 11.6 g of the desired compound as a colorless oil. After cooling extracted with ethyl acetate The extract was washed with water dried evaporated The residue was chromatographed on silica gel using 50% chloroform-n-hexane as an eluent

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 10.0 g of 5-fluoro-2-methoxyphenol, 52.9 g of ethylenebromide and 14.6 g of potassium carbonate in 50 ml of N,N-dimethylformamide was heated for 11 hours at 80° C. After cooling, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, dried and evaporated. The residue was chromatographed on silica gel using 50% chloroform-n-hexane as an eluent to give 11.6 g of the desired compound as a colorless oil. After cooling extracted with ethyl acetate The extract was washed with water dried evaporated The residue was chromatographed on silica gel using 50% chloroform-n-hexane as an eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of AlCl3 (1.17 g; 8.79 mmol) in 1,2-dichloroethane (2 mL) was added acetyl chloride (0.55 g; 7.03 mmol). After 10 min stirring was added dropwise a solution of 5-fluoro-2-methoxyphenol (0.50 g; 3.52 mmol) in 1,2-dichloroethane (2 mL). The reaction mixture was stirred overnight at 40° C. The mixture was then poured on iced water and extracted with diethylether. The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated to afford 582 mg (90%) of the title compound as an off-white solid. The reaction mixture was stirred overnight at 40° C extracted with diethylether washed with brine dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of AlCl3 (1.17 g; 8.79 mmol) in 1,2-dichloroethane (2 mL) was added acetyl chloride (0.55 g; 7.03 mmol). After 10 min stirring was added dropwise a solution of 5-fluoro-2-methoxyphenol (0.50 g; 3.52 mmol) in 1,2-dichloroethane (2 mL). The reaction mixture was stirred overnight at 40° C. The mixture was then poured on iced water and extracted with diethylether. The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated to afford 582 mg (90%) of the title compound as an off-white solid. The reaction mixture was stirred overnight at 40° C extracted with diethylether washed with brine dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxy-5-fluorophenol (226 mg, 1.59 mmol) in dimethylsulfoxide (10 mL) was added 2,4,5-trifluorobenzonitrile (250 mg, 1.59 mmol) and potassium carbonate (220 mg, 1.59 mmol) This suspension was stirred for 18 hours at room temperature. The reaction mixture was poured in saturated aqueous ammonium chloride solution (20 mL), and extracted with dichloromethane (3×40 mL). The combined organic layers were dried over sodium sulphate, and evaporated to afford the title compound as a clear oil (444 mg, 100%). This was used in the next reaction with no further purification. extracted with dichloromethane (3×40 mL) The combined organic layers were dried over sodium sulphate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methoxy-5-fluorophenol (226 mg, 1.59 mmol) in dimethylsulfoxide (10 mL) was added 2,4,5-trifluorobenzonitrile (250 mg, 1.59 mmol) and potassium carbonate (220 mg, 1.59 mmol) This suspension was stirred for 18 hours at room temperature. The reaction mixture was poured in saturated aqueous ammonium chloride solution (20 mL), and extracted with dichloromethane (3×40 mL). The combined organic layers were dried over sodium sulphate, and evaporated to afford the title compound as a clear oil (444 mg, 100%). This was used in the next reaction with no further purification. extracted with dichloromethane (3×40 mL) The combined organic layers were dried over sodium sulphate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% disp. oil, 0.281 g) was added to a solution of 5-fluoro-2-methoxyphenol (1.0 g) in DMF (20 ml) and stirred at RT for 30 min. 2-Chloro-1-fluoro-4-nitrobenzene (1.23 g) was added and the mixture stirred at RT for 16 h then diluted with water and extracted with diethylether. The organics were dried and evaporated under reduced pressure, yield 1.95 g. the mixture stirred at RT for 16 h extracted with diethylether The organics were dried evaporated under reduced pressure, yield 1.95 g