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

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

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

Procedure: 1 ml of 4-tert-butylbenzaldehyde (6.15 mmol) and 960 mg of [rac]-2-amino-1-(4-chloro -phenyl)-ethanol (estimated 4.1 mmol) were dissolved in 40 ml methanol at rt, and after stirring for 5 min at rt, were refluxed for 2 h. After cooling down to rt, 310 mg (8.2 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 a small quantity of diethylether/heptane, filtered and the solid dried under high vacuo, leading to 723 g of [rac]-(4-tert-butyl-benzyl)-[2-(4-chloro-phenyl)-2-hydroxy-ethyl]-amine as a white solid (55%). MS (ISP) 318.2 (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 a small quantity of diethylether/heptane filtered the solid dried under high vacuo

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

Procedure: A solution of 2-amino-1-(4-chlorophenyl)ethanol (1000 mg, 5.83 mmol) and (S)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (1280 mg, 5.83 mmol) in THF (20 ml) was added N,N′-methanediylidenedicyclohexanamine (1.1 eq, 1322 mg, 6.41 mmol) and allowed to stir at ambient temperature for 12 hours. Concentrate in vacuo, dilute w/EtOAc, filter washing w/EtOAc, wash w/water, brine, concentrate in vacuo. Used crude directly in the next step. 2 g of white solid. HRMS(B) tR=1.04 min; MS m/z 373.1 Concentrate in vacuo dilute w/EtOAc filter washing wash w/water, brine concentrate in vacuo

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

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

Procedure: A solution of 2-amino-1-(4-chlorophenyl)ethanol (1000 mg, 5.83 mmol) and (S)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (1280 mg, 5.83 mmol) in THF (20 ml) was added N,N′-methanediylidenedicyclohexanamine (1.1 eq, 1322 mg, 6.41 mmol) and allowed to stir at ambient temperature for 12 hours. Concentrate in vacuo, dilute w/EtOAc, filter washing w/EtOAc, wash w/water, brine, concentrate in vacuo. Used crude directly in the next step. 2 g of white solid. HRMS(B) tR=1.04 min; MS m/z 373.1 Concentrate in vacuo dilute w/EtOAc filter washing wash w/water, brine concentrate in vacuo

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

Procedure: Following a procedure similar to that described in Example 12, but using 2 g of 2-amino-1-(4-chlorophenyl)ethanol (prepared as described in Preparation 12), 3.11 g of methyl 4-(2-oxopropoxy)phenylacetate (prepared as described in Preparation 3), 60 ml of benzene, 50 ml of absolute methanol and 2.7 g of sodium cyanoborohydride, 1.54 g of the title compound were obtained as crystals, melting at 78°-79° C.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(4-(3-carbomethoxyprop-2-eneoxy) phenyl) propan-2-one (2.27 g) and 2-hydroxy-2-(4-chlorophenyl) ethanamine (1.57 g) in benzene (100 ml) was boiled under reflux with azeotropic removal of water using a Dean and Stark trap. The solution was evaporated, the residue dissolved in methanol (50 ml), cooled in ice and sodium borohydride added. The solution was stirred for 1 hour at 0° C., the methanol evaporated, and the residue partitioned between water and ethyl acetate. The ethyl acetate layer was dried (MgSO4) and evaporated to give a cream solid (3.1 g) which was crystallised from ethyl acetate m.p. 120°-122°. as a 0:100 mixture of diastereoisomers. Recrystallisation of the mother liquors from hexane gave a 70:30 mixture of diastereoisomers, m.p. 55°-65°. The solution was evaporated the residue dissolved in methanol (50 ml) cooled in ice sodium borohydride added the methanol evaporated the residue partitioned between water and ethyl acetate The ethyl acetate layer was dried (MgSO4) evaporated

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

Procedure: Following a procedure similar to that described in Example 12, but using 2 g of 2-amino-1-(4-chlorophenyl)ethanol (prepared as described in Preparation 12), 3.11 g of methyl 4-(2-oxopropoxy)phenylacetate (prepared as described in Preparation 3), 60 ml of benzene, 50 ml of absolute methanol and 2.7 g of sodium cyanoborohydride, 1.54 g of the title compound were obtained as crystals, melting at 78°-79° C.

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

Procedure: To 5.2 parts of 2-(nitramino)-2-imidazoline is added a solution of 7.5 parts of α-(aminomethyl)-p-chlorobenzyl alcohol in 40 parts of xylene while heating. Upon completion, stirring is continued while heating in an oil-bath at 150°-160°C. and while the xylene is partly distilled off (till gas evolution ceases). The residue is cooled and after the addition of a few parts of acetone, the produce is allowed to crystallize. It is filtered off, washed successively with acetone and diisopropylether, dried and the product is recrystallized from 4-methyl-2-pentanone, yielding p-chloro-α-(2-imidazolin-2-ylaminomethyl)benzyl alcohol; m.p. 156°-158°C. while heating is partly distilled off (till gas evolution ceases) The residue is cooled after the addition of a few parts of acetone to crystallize It is filtered off washed successively with acetone and diisopropylether dried the product is recrystallized from 4-methyl-2-pentanone

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

Procedure: To 5.2 parts of 2-(nitramino)-2-imidazoline is added a solution of 7.5 parts of α-(aminomethyl)-p-chlorobenzyl alcohol in 40 parts of xylene while heating. Upon completion, sitrring is continued while heating in an oil-bath at 150°-160°C. and while the xylene is partly distilled off (till gas evolution ceases). The residue is cooled and after the addition of a few parts of acetone, the product is allowed to crystallize. It is filtered off, washed successively with acetone and diisopropylether, dried and the product is recrystallized from 4-methyl-2-pentanone, yielding p-chloro-α-(2-imidazolin-2-ylaminomethyl)benzyl alcohol; m.p. 156°-158°C. while heating is partly distilled off (till gas evolution ceases) The residue is cooled after the addition of a few parts of acetone to crystallize It is filtered off washed successively with acetone and diisopropylether dried the product is recrystallized from 4-methyl-2-pentanone

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

Procedure: 1 ml of 4-tert-butylbenzaldehyde (6.15 mmol) and 960 mg of [rac]-2-amino-1-(4-chloro -phenyl)-ethanol (estimated 4.1 mmol) were dissolved in 40 ml methanol at rt, and after stirring for 5 min at rt, were refluxed for 2 h. After cooling down to rt, 310 mg (8.2 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 a small quantity of diethylether/heptane, filtered and the solid dried under high vacuo, leading to 723 g of [rac]-(4-tert-butyl-benzyl)-[2-(4-chloro-phenyl)-2-hydroxy-ethyl]-amine as a white solid (55%). MS (ISP) 318.2 (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 a small quantity of diethylether/heptane filtered the solid dried under high vacuo

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

Procedure: A solution of 2-amino-1-(4-chlorophenyl)ethanol (1000 mg, 5.83 mmol) and (S)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (1280 mg, 5.83 mmol) in THF (20 ml) was added N,N′-methanediylidenedicyclohexanamine (1.1 eq, 1322 mg, 6.41 mmol) and allowed to stir at ambient temperature for 12 hours. Concentrate in vacuo, dilute w/EtOAc, filter washing w/EtOAc, wash w/water, brine, concentrate in vacuo. Used crude directly in the next step. 2 g of white solid. HRMS(B) tR=1.04 min; MS m/z 373.1 Concentrate in vacuo dilute w/EtOAc filter washing wash w/water, brine concentrate in vacuo