methyl 4-(2-aminoethyl)benzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chlorophenylglyoxal (1.6 g) and 2-(4-carbomethoxyphenyl)ethanamine (1.8 g) were heated in refluxing benzene (100 ml) under a Dean and Stark head until the theoretical amount of water had been collected. The solvent was replaced with methanol (100 ml) and sodium borohydride (2.5 g) was added portionwise with ice cooling. The mixture was stirred for 2 h, the solvent was evaporated and the residue was paritioned between water (100 ml) and chloroform (100 ml). The dried organic extract was evaporated and crystallised from methanol to give a single diastereoisomer m.p. 94°-96° (0.19 g) (less active diasteroisomer). had been collected was added portionwise with ice cooling the solvent was evaporated The dried organic extract was evaporated crystallised from methanol to give a single diastereoisomer m.p. 94°-96° (0.19 g) (less active diasteroisomer)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chlorophenylglyoxal (1.6 g) and 2-(4-carbomethoxyphenyl)ethanamine (1.8 g) were heated in refluxing benzene (100 ml) under a Dean and Stark head until the theoretical amount of water had been collected. The solvent was replaced with methanol (100 ml) and sodium borohydride (2.5 g) was added portionwise with ice cooling. The mixture was stirred for 2 h, the solvent was evaporated and the residue was paritioned between water (100 ml) and chloroform (100 ml). The dried organic extract was evaporated and crystallised from methanol to give a single diastereoisomer m.p. 94°-96° (0.19 g) (less active diasteroisomer). had been collected was added portionwise with ice cooling the solvent was evaporated The dried organic extract was evaporated crystallised from methanol to give a single diastereoisomer m.p. 94°-96° (0.19 g) (less active diasteroisomer)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared as in Example 1a from 3-trifluoromethylphenyl glyoxal (3.85 g) and 2-(4-carbomethoxyphenyl) ethanamine (3.4 g), and crystallised from hexane m.p. 75-77.5. τ(CDCl3) 7.66 (2H, broad, replaceable by D2O), 5.9-6.5 (6H, m), 6.15 (3H,s), 5.3 (1H,m), 2.75 (2H,d,J=8 Hz), 2.3-2.6 (4H,m), 2.03 (2H,d,J=8 Hz). crystallised from hexane m.p. 75-77.5

反応条件: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.02 g (10.0 mmol) of 4-(2-aminoethyl)benzoic acid hydrochloride in 25 mL of methanol was added 1.5 mL of H2SO4. The mixture was heated to reflux and became a homogeneous solution after 1 h. The solution was refluxed for about 16 h, cooled to 22° C. and concentrated to about 10 mL by evaporation. The solution was diluted with 100 mL of water, made basic with 1 N NaOH and extracted with 100 mL of dichloromethane (DCM). The aqueous layer was back-extracted with DCM (4×100 mL). The combined extracts were dried (Na2SO4) and evaporated to give methyl 4-(2-aminoethyl)benzoate as a colorless oil. The material was used directly in the subsequent transformation. The mixture was heated to reflux after 1 h The solution was refluxed for about 16 h concentrated to about 10 mL by evaporation The solution was diluted with 100 mL of water extracted with 100 mL of dichloromethane (DCM) The aqueous layer was back-extracted with DCM (4×100 mL) The combined extracts were dried (Na2SO4) evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared as a mixture of diastereoisomers by the process of Example 25, replacing phenyl glyoxal by 4-benzyloxy-3-nitrophenyl glyoxal and 2-(4-carbomethoxyphenyl)ethanamine by 2-(4-carbomethoxyphenyl)-1-methylethanamine. τ (CDCl3) 8.93 (3H, d, J=6 Hz), 6.70-7.80 (7H, m), 6.14 (3H, s), 5.40 (1H, m), 4.81 (2H, s) 2.30-3.10 (10H, m), 2.02 (2H, d, J=8 Hz).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by the process of Example 25, replacing phenyl glyoxal by 4-benzyloxy-3-hydroxymethylphenyl glyoxal and 2-(4-carbomethoxyphenyl)ethanamine by 2-(4-carbomethoxyphenyl)-1,1-dimethylethanamine. τ (d6DMSO) 9.06 (6H, s), 7.10-7.60 (5H, m), 6.20 (3H, s), 5.39 (2H, s), 5.00 (1H, m), 4.88 (2H, s), 3.04 (2H, d, J=8 Hz), 2.40-3.00 (10H, m), 2.12 (2H, d, J=8 Hz).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Phenyl glyoxal (0.8 g) and 2-(4-carbomethoxyphenyl)ethanamine (1.1 g) were heated in refluxing benzene (100 ml) under a Dean and stark head until the theoretical amount of water had been collected. The solvent was replaced with methanol and sodium borohydride (2.0 g) was added portionwise with ice cooling. The mixture was stirred for 2 hours, the solvent was evaporated and the residue was partitioned between water and ethyl acetate. The dried organic extract was evaporated and crystallised from benzene/hexane, mp 105°-106°. (CDCl3) 6.80-7.60 (8H, m), 6.18 (3H, s), 5.34 (1H, m), 2.94 (2H, d, J=8 Hz), 2.77 (5H, m), 2.09 (2H, d, J=8 Hz). had been collected was added portionwise with ice cooling the solvent was evaporated the residue was partitioned between water and ethyl acetate The dried organic extract was evaporated crystallised from benzene/hexane, mp 105°-106°

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Palladium on carbon (10%, 50 mg) was added to a solution of 4-(2-nitrovinyl)benzoic acid methyl ester (228 mg) in 5 mL of ethyl alcohol and 2 mL of acetic acid. The reaction vessel was saturated with hydrogen and stirred under a 1 atm hydrogen atmosphere for 20 h. The vessel was saturated with nitrogen and filtered through celite. Evaporation of the solvents gave 205 mg of crude 4-(2-amino-ethyl)-benzoic acid methyl ester. filtered through celite Evaporation of the solvents

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Palladium on carbon (10%, 50 mg) was added to a solution of 4-(2-nitrovinyl)benzoic acid methyl ester (228 mg) in 5 mL of ethyl alcohol and 2 mL of acetic acid. The reaction vessel was saturated with hydrogen and stirred under a 1 atm hydrogen atmosphere for 20 h. The vessel was saturated with nitrogen and filtered through celite. Evaporation of the solvents gave 205 mg of crude 4-(2-amino-ethyl)-benzoic acid methyl ester. filtered through celite Evaporation of the solvents

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Using methyl 4-(2-aminoethyl)benzoate (0.78 g) and 3-chloropropane-1-sulfonyl chloride (0.69 mL) and by the reaction and treatment in the same manner as in Preparation Example 17, the title compound (1.00 g) was obtained. by the reaction and treatment in the same manner as in Preparation Example 17

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared as a mixture of diastereoisomers by the process of Example 25, replacing phenyl glyoxal by 4-benzyloxy-3-nitrophenyl glyoxal and 2-(4-carbomethoxyphenyl)ethanamine by 2-(4-carbomethoxyphenyl)-1-methylethanamine. τ(CDCl3) 8.93 (3H, d, J=6 Hz), 6.70-7.80 (7H, m), 6.14 (3H, s), 5.40 (1H, m), 4.81 (2H, s) 2.30-3.10 (10H, m), 2.02 (2H, d, J=8 Hz).