methyl (E)-3-(2-amino-4-chlorophenyl)prop-2-enoate

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

Procedure: To a stirred solution of methyl trans-2-amino-4-chlorocinnamate (R. W. Carling et al., J. Med. Chem. 1993, 36, 3397., 32.6 g, 0.15 mol), pyridine (14.9 ml, 0.17 mol) and 4-dimethylaminopridine (0.5 g) in dichloromethane (500 ml) was added dropwise ethyl chloroformate (16.2 ml, 0.17 mol) at room temperature. After stirring for 2h, the mixture was concentrated. The residue was diluted in ethyl acetate (1000 ml) and washed with 10% aqueous citric acid (500 ml). The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml). After drying (MgSO4) and removal of solvent, the residual solids were recrystallized from ethyl acetate/hexane to give 39.13 g (92%) of the title compound. the mixture was concentrated The residue was diluted in ethyl acetate (1000 ml) washed with 10% aqueous citric acid (500 ml) The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml) After drying (MgSO4) and removal of solvent the residual solids were recrystallized from ethyl acetate/hexane

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

Procedure: To a solution of methyl trans-4-chloro-2-aminocinnamate (R. W. Carling et al., J.Med.Chem., 1993, 36, 3397., 30.7 g, 0.15 mol) and pyridine (36 ml, 0.45 mol) in dichloromethane (500 ml) was added benzenesulfonyl chloride (20 ml, 0.16 mol). After stirring for 20 h, methanol (50 ml) was added and the mixture was concentrated. The residual solids were dissolved in dichloromethane (700 ml) and washed with 2N aqueous HCl (150 ml), brine (150 ml) and dried (MgSO4). After removal of solvent, the residual solids were recrystallized from ethanol to give 40 g (76%) of the title compound as pale yellow solids. the mixture was concentrated The residual solids were dissolved in dichloromethane (700 ml) washed with 2N aqueous HCl (150 ml), brine (150 ml) dried (MgSO4) After removal of solvent the residual solids were recrystallized from ethanol

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

Procedure: To a stirred solution of methyl trans-2-amino-4-chlorocinnamate (R. W. Carling et al., J. Med. Chem. 1993, 36, 3397., 32.6 g, 0.15 mol), pyridine (14.9 ml, 0.17 mol) and 4-dimethylaminopridine (0.5 g) in dichloromethane (500 ml) was added dropwise ethyl chloroformate (16.2 ml, 0.17 mol) at room temperature. After stirring for 2h, the mixture was concentrated. The residue was diluted in ethyl acetate (1000 ml) and washed with 10% aqueous citric acid (500 ml). The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml). After drying (MgSO4) and removal of solvent, the residual solids were recrystallized from ethyl acetate/hexane to give 39.13 g (92%) of the title compound. the mixture was concentrated The residue was diluted in ethyl acetate (1000 ml) washed with 10% aqueous citric acid (500 ml) The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml) After drying (MgSO4) and removal of solvent the residual solids were recrystallized from ethyl acetate/hexane

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

Procedure: To a stirred solution of methyl trans-2-amino-4-chlorocinnamate (R. W. Carling et al., J. Med. Chem. 1993, 36, 3397., 32.6 g, 0.15 mol), pyridine (14.9 ml, 0.17 mol) and 4-dimethylaminopridine (0.5 g) in dichloromethane (500 ml) was added dropwise ethyl chloroformate (16.2 ml, 0.17 mol) at room temperature. After stirring for 2h, the mixture was concentrated. The residue was diluted in ethyl acetate (1000 ml) and washed with 10% aqueous citric acid (500 ml). The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml). After drying (MgSO4) and removal of solvent, the residual solids were recrystallized from ethyl acetate/hexane to give 39.13 g (92%) of the title compound. the mixture was concentrated The residue was diluted in ethyl acetate (1000 ml) washed with 10% aqueous citric acid (500 ml) The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml) After drying (MgSO4) and removal of solvent the residual solids were recrystallized from ethyl acetate/hexane

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

Procedure: To a solution of methyl trans-4-chloro-2-aminocinnamate (R. W. Carling et al., J.Med.Chem., 1993, 36, 3397., 30.7 g, 0.15 mol) and pyridine (36 ml, 0.45 mol) in dichloromethane (500 ml) was added benzenesulfonyl chloride (20 ml, 0.16 mol). After stirring for 20 h, methanol (50 ml) was added and the mixture was concentrated. The residual solids were dissolved in dichloromethane (700 ml) and washed with 2N aqueous HCl (150 ml), brine (150 ml) and dried (MgSO4). After removal of solvent, the residual solids were recrystallized from ethanol to give 40 g (76%) of the title compound as pale yellow solids. the mixture was concentrated The residual solids were dissolved in dichloromethane (700 ml) washed with 2N aqueous HCl (150 ml), brine (150 ml) dried (MgSO4) After removal of solvent the residual solids were recrystallized from ethanol

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-3-(2-Amino-4-chlorophenyl)-acrylic acid methyl ester (Carling, Robert W.; et al. J. Med. Chem. (1993), 36(22), 3397-408) (3.3 g, 15.6 mmol) in THF (63 ml) was combined with (BOC)2O (6.8 g, 31.2 mmol) and refluxed for 4 hours. THF was evaporated and a second portion of (BOC)2O added (6.8 g, 31.2 mmol). The mixture was heated to 100° C. for 18 hours. Recrystallisation from TBME/hexanes rendered the title compound as colorless crystals (4.6 g; 94%). refluxed for 4 hours THF was evaporated a second portion of (BOC)2O added (6.8 g, 31.2 mmol) Recrystallisation from TBME/hexanes

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

Procedure: To a stirred solution of methyl trans-2-amino-4-chlorocinnamate (R. W. Carling et al., J. Med. Chem. 1993, 36, 3397., 32.6 g, 0.15 mol), pyridine (14.9 ml, 0.17 mol) and 4-dimethylaminopridine (0.5 g) in dichloromethane (500 ml) was added dropwise ethyl chloroformate (16.2 ml, 0.17 mol) at room temperature. After stirring for 2h, the mixture was concentrated. The residue was diluted in ethyl acetate (1000 ml) and washed with 10% aqueous citric acid (500 ml). The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml). After drying (MgSO4) and removal of solvent, the residual solids were recrystallized from ethyl acetate/hexane to give 39.13 g (92%) of the title compound. the mixture was concentrated The residue was diluted in ethyl acetate (1000 ml) washed with 10% aqueous citric acid (500 ml) The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml) After drying (MgSO4) and removal of solvent the residual solids were recrystallized from ethyl acetate/hexane

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

Procedure: To a solution of methyl trans-4-chloro-2-aminocinnamate (R. W. Carling et al., J.Med.Chem., 1993, 36, 3397., 30.7 g, 0.15 mol) and pyridine (36 ml, 0.45 mol) in dichloromethane (500 ml) was added benzenesulfonyl chloride (20 ml, 0.16 mol). After stirring for 20 h, methanol (50 ml) was added and the mixture was concentrated. The residual solids were dissolved in dichloromethane (700 ml) and washed with 2N aqueous HCl (150 ml), brine (150 ml) and dried (MgSO4). After removal of solvent, the residual solids were recrystallized from ethanol to give 40 g (76%) of the title compound as pale yellow solids. the mixture was concentrated The residual solids were dissolved in dichloromethane (700 ml) washed with 2N aqueous HCl (150 ml), brine (150 ml) dried (MgSO4) After removal of solvent the residual solids were recrystallized from ethanol