2-amino-1-(4-fluorophenyl)ethanol

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:; See reaction.notes.procedure_details.

Procedure: 0.52 ml of 4-tert-butylbenzaldehyde (3.1 mmol) and 320 mg of [rac]-2-amino-1-(4-fluoro-phenyl)-ethanol (2.06 mmol) were dissolved in 15 ml methanol at rt, and after stirring for 5 min at rt, were refluxed for 2 h. After cooling down to rt, 117 mg (3.1 mmol) of sodium borohydride were added and after stirring for 15 min at rt, the reaction mixture was then refluxed for 2 h. After cooling down to rt, the residue was diluted with water/EtOAc. After separation of the organic phase, the aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried with magnesium sulfate, filtered off and concentrated in vacuo. The residue was stirred with diethylether/heptane, filtered and the solid dried under high vacuo, leading to 410 mg of [rac]-(4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amine as a white solid (66%). MS (ISP) 302.2 (M+H)+. were refluxed for 2 h After cooling down to rt after stirring for 15 min at rt the reaction mixture was then refluxed for 2 h After cooling down to rt After separation of the organic phase the aqueous phase was extracted with EtOAc the combined organic phases were washed with brine dried with magnesium sulfate filtered off concentrated in vacuo The residue was stirred with diethylether/heptane filtered the solid dried under high vacuo

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

Procedure: 0.52 ml of 4-tert-butylbenzaldehyde (3.1 mmol) and 320 mg of [rac]-2-amino-1-(4-fluoro-phenyl)-ethanol (2.06 mmol) were dissolved in 15 ml methanol at rt, and after stirring for 5 min at rt, were refluxed for 2 h. After cooling down to rt, 117 mg (3.1 mmol) of sodium borohydride were added and after stirring for 15 min at rt, the reaction mixture was then refluxed for 2 h. After cooling down to rt, the residue was diluted with water/EtOAc. After separation of the organic phase, the aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried with magnesium sulfate, filtered off and concentrated in vacuo. The residue was stirred with diethylether/heptane, filtered and the solid dried under high vacuo, leading to 410 mg of [rac]-(4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amine as a white solid (66%). MS (ISP) 302.2 (M+H)+. were refluxed for 2 h After cooling down to rt after stirring for 15 min at rt the reaction mixture was then refluxed for 2 h After cooling down to rt After separation of the organic phase the aqueous phase was extracted with EtOAc the combined organic phases were washed with brine dried with magnesium sulfate filtered off concentrated in vacuo The residue was stirred with diethylether/heptane filtered the solid dried under high vacuo

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

Procedure: A recovery flask was charged with 520 mg (2.81 mmol) of the optically active 1-(4-fluorophenyl)-2-nitroethanol obtained in Example 14, 52 mg of 10% Pd/C, and 2.8 ml of methanol, and stirring was carried out under an atmosphere of hydrogen at atmospheric pressure and 30° C. for 22 hours. After the reaction was completed, the catalyst was filtered off and the solvent was distilled off under vacuum to give 421 mg (yield 97%, 1H-NMR) of optically active 2-amino-1-(4-fluorophenyl)ethanol as white crystals. The amino group of the amino alcohol so obtained was monobenzoylated by reaction with benzoyl chloride, and when it was analyzed using a CHIRALCEL OD column (eluant; n-hexane:2-propanol=30:1), it was found that the optical purity was 96% ee. the catalyst was filtered off the solvent was distilled off under vacuum

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

Procedure: To a solution consisting of 2-amino-1-(4-fluoro-phenyl)-ethanone (150 mg, 0.9 mmol) and MeOH (5 mL) was added NaBH4 (97 mg, 2.6 mmol). The mixture was stirred at rt for 45 min and then concentrated to dryness. The residue was diluted with EtOAc and washed with a satd. NH4Cl solution before drying (Na2SO4), and concentrating to give 2-amino-1-(4-fluoro-phenyl)-ethanol (139 mg, 100%) which was used without further purification. concentrated to dryness The residue was diluted with EtOAc washed with a satd NH4Cl solution before drying (Na2SO4) concentrating

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6.5 parts of α-(aminomethyl)-p-fluorobenzyl alcohol in 8 parts of xylene are added 5.2 parts of 2-(nitramino)-2-imidazoline. The mixture is heated in an oil-bath to about 160°C. till gas-evolution is ceased (about 15 minutes). The reaction mixture is cooled and treated with benzene and acetone. The product is sucked off and crystallized from 4-methyl-2-pentanone, yielding p-fluoro-α-(2-imidazolin-2-ylaminomethyl)benzyl alcohol; m.p. 153.4°C. (about 15 minutes) The reaction mixture is cooled crystallized from 4-methyl-2-pentanone

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6.5 parts of α-(aminomethyl)-p-fluorobenzyl alcohol in 8 parts of xylene are added 5.2 parts of 2-(nitramino)-2-imidazoline. The mixture is heated in an oil-bath to about 160°C. till gas-evolution is ceased (about 15 minutes). The reaction mixture is cooled and treated with benzene and acetone. The product is sucked off and crystallized from 4-methyl-2-pentanone, yielding p-fluoro-α-(2-imidazolin-2-ylaminomethyl)benzyl alcohol; m.p. 153.4°C. (about 15 minutes) The reaction mixture is cooled crystallized from 4-methyl-2-pentanone

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

Procedure: Sodium cyanoborohydride (0.62 mL, 1 M in THF) was added to a solution of 2-amino-1-(4-fluoro-phenyl)-ethanol (80 mg, 0.52 mmol), 4-(Pyrazin-2-yloxy)-benzaldehyde (103 mg, 0.52 mmol) and glacial acetic acid (0.5 mL), in methanol (3 mL) at RT and the flask was stirred overnight. The reaction mixture was concentrated in vacuo; the residue was quenched with saturated aqueous sodium bicarbonate solution and then extracted with dichloromethane (3×4 mL). The combined organic phases were dried over anhydrous sodium sulfate and concentrated again in vacuo to yield 1-(4-fluoro-phenyl)-2-[4(pyrazin-2-yloxy)-benzyl amino]-ethanol as a white solid 62 mg, 35%). The reaction mixture was concentrated in vacuo the residue was quenched with saturated aqueous sodium bicarbonate solution extracted with dichloromethane (3×4 mL) The combined organic phases were dried over anhydrous sodium sulfate concentrated again in vacuo

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

Procedure: 0.52 ml of 4-tert-butylbenzaldehyde (3.1 mmol) and 320 mg of [rac]-2-amino-1-(4-fluoro-phenyl)-ethanol (2.06 mmol) were dissolved in 15 ml methanol at rt, and after stirring for 5 min at rt, were refluxed for 2 h. After cooling down to rt, 117 mg (3.1 mmol) of sodium borohydride were added and after stirring for 15 min at rt, the reaction mixture was then refluxed for 2 h. After cooling down to rt, the residue was diluted with water/EtOAc. After separation of the organic phase, the aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried with magnesium sulfate, filtered off and concentrated in vacuo. The residue was stirred with diethylether/heptane, filtered and the solid dried under high vacuo, leading to 410 mg of [rac]-(4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-amine as a white solid (66%). MS (ISP) 302.2 (M+H)+. were refluxed for 2 h After cooling down to rt after stirring for 15 min at rt the reaction mixture was then refluxed for 2 h After cooling down to rt After separation of the organic phase the aqueous phase was extracted with EtOAc the combined organic phases were washed with brine dried with magnesium sulfate filtered off concentrated in vacuo The residue was stirred with diethylether/heptane filtered the solid dried under high vacuo