(4-amino-2-fluorophenyl)methanol

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 ml three necked round bottom flask, methyl 4-amino-2-fluorobenzoate (2.75 g, 0.0162 mole) was added in anhydrous THF (60 ml) under nitrogen atmosphere and cooled to 0-5° C. After 15 minutes, 2.0 M solutions of LAH in THF (24.3 ml, 0.0487 mole) was added dropwise and stirred for 10 min. The reaction mixture was allowed to warm up to room temperature and stirred at same temperature for 1 hr. After completion of the reaction, the reaction mixture was cooled to 5° C. and quenched with sat. NH4Cl (25 ml) and diluted with water (100 ml) followed by extraction with ethyl acetate. The combined organics were washed with water, dried over sodium sulphate and evaporated to afford brown solid (crude) product which was purified using column purification by eluting the compound with 20% ethyl acetate in hexanes to yield 1.7 g of (4-amino-2-fluorophenyl)methanol. to warm up to room temperature stirred at same temperature for 1 hr After completion of the reaction the reaction mixture was cooled to 5° C. quenched with sat. NH4Cl (25 ml) diluted with water (100 ml) followed by extraction with ethyl acetate The combined organics were washed with water dried over sodium sulphate evaporated to afford brown solid (crude) product which was purified column purification by eluting the compound with 20% ethyl acetate in hexanes

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 ml three necked round bottom flask, methyl 4-amino-2-fluorobenzoate (2.75 g, 0.0162 mole) was added in anhydrous THF (60 ml) under nitrogen atmosphere and cooled to 0-5° C. After 15 minutes, 2.0 M solutions of LAH in THF (24.3 ml, 0.0487 mole) was added dropwise and stirred for 10 min. The reaction mixture was allowed to warm up to room temperature and stirred at same temperature for 1 hr. After completion of the reaction, the reaction mixture was cooled to 5° C. and quenched with sat. NH4Cl (25 ml) and diluted with water (100 ml) followed by extraction with ethyl acetate. The combined organics were washed with water, dried over sodium sulphate and evaporated to afford brown solid (crude) product which was purified using column purification by eluting the compound with 20% ethyl acetate in hexanes to yield 1.7 g of (4-amino-2-fluorophenyl)methanol. to warm up to room temperature stirred at same temperature for 1 hr After completion of the reaction the reaction mixture was cooled to 5° C. quenched with sat. NH4Cl (25 ml) diluted with water (100 ml) followed by extraction with ethyl acetate The combined organics were washed with water dried over sodium sulphate evaporated to afford brown solid (crude) product which was purified column purification by eluting the compound with 20% ethyl acetate in hexanes

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

Procedure: To a stirred solution of (4-amino-2-fluorophenyl)methanol (100 mg, 0.709 mmol, 1 eq.) in acetone (1.0 mL) was added pyridine (0.17 mL, 2.12 mmol, 3 eq.) followed by phenyl chloroformate (0.092 mL, 0.709 mmol, 1 eq.) at 0° C. and stirred at RT for 1 h. The solvent was evaporated and the residue obtained was purified by CC using ethyl acetate/PE (7:13) as eluent to get phenyl 3-fluoro-4-(hydroxymethyl)phenylcarbamate (110 mg, 60%, off-white solid; TLC system: EtOAc/PE (1:1), Rf: 0.4). The solvent was evaporated the residue obtained was purified by CC

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

Procedure: To a stirred solution of (2-fluoro-4-nitrophenyl)methanol (3.0 g, 1.0 eq.) in EtOAc (30 mL) was added 10% Pd—C and the reaction mixture was stirred under H2 gas balloon at RT for 6 h. The reaction mixture was passed through a celite pad and the solvent evaporated. The residue was purified by neutral alumina column using PE/EtOAc (3:2) as eluent to get (4-amino-2-fluorophenyl)methanol (1.1 g, 48%) as a solid; TLC system: EtOAc/PE (1:1), Rf: 0.3). the solvent evaporated The residue was purified by neutral alumina column

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

Procedure: To a stirred solution of (4-amino-2-fluorophenyl)methanol (100 mg, 0.709 mmol, 1 eq.) in acetone (1.0 mL) was added pyridine (0.17 mL, 2.12 mmol, 3 eq.) followed by phenyl chloroformate (0.092 mL, 0.709 mmol, 1 eq.) at 0° C. and stirred at RT for 1 h. The solvent was evaporated and the resulting residue was purified by CC using ethyl acetate/PE (7:13) as eluent to get phenyl 3-fluoro-4-(hydroxymethyl)phenylcarbamate (110 mg, 60%, off-white solid; TLC system: EtOAc/PE (1:1), Rf: 0.4). The solvent was evaporated the resulting residue was purified by CC

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

Procedure: To a stirred solution of (2-fluoro-4-nitrophenyl)methanol (3.0 g, 1.0 eq.) in EtOAc (30 mL) was added 10% Pd—C and the reaction mixture was stirred under H2 gas balloon at RT for 6 h. The reaction mixture was passed through a celite pad and the solvent evaporated. The residue was purified by neutral alumina column using PE/EtOAc (3:2) as eluent to get (4-amino-2-fluorophenyl)methanol (1.1 g, 48%) as a solid; TLC system: EtOAc/PE (1:1), Rf: 0.3). the solvent evaporated The residue was purified by neutral alumina column

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 ml three necked round bottom flask, methyl 4-amino-2-fluorobenzoate (2.75 g, 0.0162 mole) was added in anhydrous THF (60 ml) under nitrogen atmosphere and cooled to 0-5° C. After 15 minutes, 2.0 M solutions of LAH in THF (24.3 ml, 0.0487 mole) was added dropwise and stirred for 10 min. The reaction mixture was allowed to warm up to room temperature and stirred at same temperature for 1 hr. After completion of the reaction, the reaction mixture was cooled to 5° C. and quenched with sat. NH4Cl (25 ml) and diluted with water (100 ml) followed by extraction with ethyl acetate. The combined organics were washed with water, dried over sodium sulphate and evaporated to afford brown solid (crude) product which was purified using column purification by eluting the compound with 20% ethyl acetate in hexanes to yield 1.7 g of (4-amino-2-fluorophenyl)methanol. to warm up to room temperature stirred at same temperature for 1 hr After completion of the reaction the reaction mixture was cooled to 5° C. quenched with sat. NH4Cl (25 ml) diluted with water (100 ml) followed by extraction with ethyl acetate The combined organics were washed with water dried over sodium sulphate evaporated to afford brown solid (crude) product which was purified column purification by eluting the compound with 20% ethyl acetate in hexanes