(3-amino-4-fluorophenyl)methanol

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

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

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

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

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from Example 8A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C., then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled, and extracted with methylene chloride. The organic phase was washed with 10% sodium hydroxide, 1 M sodium thiosulfate, 10% hydrochloric acid, aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and the solvent evaporated. The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. to maintain the temperature below 10° C. cooled extracted with methylene chloride The organic phase was washed with 10% sodium hydroxide, 1 M sodium thiosulfate, 10% hydrochloric acid, aqueous sodium bicarbonate dried (sodium sulfate) filtered the solvent evaporated The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from Example 8A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C., then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled, and extracted with methylene chloride. The organic phase was washed with 10% sodium hydroxide, 1 M sodium thiosulfate, 10% hydrochloric acid, aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and the solvent evaporated. The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. to maintain the temperature below 10° C. cooled extracted with methylene chloride The organic phase was washed with 10% sodium hydroxide, 1 M sodium thiosulfate, 10% hydrochloric acid, aqueous sodium bicarbonate dried (sodium sulfate) filtered the solvent evaporated The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3)

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

Procedure: 3-Amino-4-fluorobenzoic acid (15 g, 97 mmol) in THF at 0° C. was treated with 1.0 M BH3•THF (50 mL) with stirring overnight at room temperature. An additional 130 mL 1.0 M BH3•THF was added with stirring for 10 hours. The reaction mixture was quenched by the addition of methanol, stirred 3 hours at room temperature, solvent evaporated, and the product partitioned between aqueous sodium bicarbonate/methylene chloride. The organic layer was dried (sodium sulfate), filtered, and the solvent evaporated. The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 1:1) to provide 7.0 g of the title compound. with stirring for 10 hours The reaction mixture was quenched by the addition of methanol stirred 3 hours at room temperature solvent evaporated the product partitioned between aqueous sodium bicarbonate/methylene chloride The organic layer was dried (sodium sulfate) filtered the solvent evaporated The crude product was purified by flash chromatography over silica gel (ethyl acetate/hexane 1:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from Example 2A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C. and then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled and extracted with methylene chloride. The methylene chloride layer was washed with 10% sodium hydroxide, washed with 1M sodium thiosulfate, washed with 10% hydrochloric acid, washed with aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated. The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. to maintain the temperature below 10° C. cooled extracted with methylene chloride The methylene chloride layer was washed with 10% sodium hydroxide washed with 1M sodium thiosulfate washed with 10% hydrochloric acid washed with aqueous sodium bicarbonate dried (sodium sulfate) filtered concentrated The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product from Example 2A (7.0 g, 50 mmol) in water (100 mL) at 0° C. was treated slowly with concentrated sulfuric acid (30 mL) at a rate to maintain the temperature below 10° C. and then treated dropwise with an aqueous solution of sodium nitrite (3.45 g, 50 mmol). This solution was then added to a solution of potassium iodide (8.13 g, 50 mmol) in water (15 mL), heated to 60° C. for 2 hours, cooled and extracted with methylene chloride. The methylene chloride layer was washed with 10% sodium hydroxide, washed with 1M sodium thiosulfate, washed with 10% hydrochloric acid, washed with aqueous sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated. The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3) to provide 6.4 g of the title compound. to maintain the temperature below 10° C. cooled extracted with methylene chloride The methylene chloride layer was washed with 10% sodium hydroxide washed with 1M sodium thiosulfate washed with 10% hydrochloric acid washed with aqueous sodium bicarbonate dried (sodium sulfate) filtered concentrated The residue was purified by flash chromatography over silica gel (ethyl acetate/hexane 7:3)

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

Procedure: 3-Amino-4-fluorobenzoic acid (15 g, 97 mmol) in tetrahydrofuran at 0° C. was treated with 1.0M borane-tetrahydrofuran complex (50 mL), stirred overnight at ambient temperature, treated with an additional 130 mL of 1.0M borane-tetrahydrofuran complex, stirred 10 hours, quenched by the addition of methanol, stirred 3 hours at ambient temperature, concentrated and partitioned between aqueous sodium bicarbonate/methylene chloride. The methylene chloride layer was separated, dried (sodium sulfate), filtered, and concentrated. The residue was purified by flash chromatography over silica gel (ethyl acetate:hexanes 1:1) to provide 7.0 g of the title compound. treated with an additional 130 mL of 1.0M borane-tetrahydrofuran complex stirred 10 hours quenched by the addition of methanol stirred 3 hours at ambient temperature concentrated partitioned between aqueous sodium bicarbonate/methylene chloride The methylene chloride layer was separated dried (sodium sulfate) filtered concentrated The residue was purified by flash chromatography over silica gel (ethyl acetate:hexanes 1:1)