methyl (1R,2R)-2-(4-aminophenyl)cyclopropane-1-carboxylate

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

Procedure: Compound 15 was synthesized from methyl (1R,2R)-2-(4-aminophenyl)cyclopropane carboxylate (0.18 g, 0.9 mmol) and 4-{[(2Z)-2-(methoxyimino)-2-(2-methylphenyl)ethyl]oxy}benzaldehyde (0.31 g, 1.1 mmol) by following the procedure described in Scheme 3 (0.12 g, yield: 28%); Purity: 91.26%.

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

Procedure: Compound 15 was synthesized from methyl (1R,2R)-2-(4-aminophenyl)cyclopropane carboxylate (0.18 g, 0.9 mmol) and 4-{[(2Z)-2-(methoxyimino)-2-(2-methylphenyl)ethyl]oxy}benzaldehyde (0.31 g, 1.1 mmol) by following the procedure described in Scheme 3 (0.12 g, yield: 28%); Purity: 91.26%.

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

Procedure: To a 25 mL RB flask fitted with magnetic stirrer was charged 5 mL of methanol: and 5 mL of THF. To the stirred solvent, was added methyl (1R,2R)-2-(4-aminophenyl)cyclo propane carboxylate (1 g, 5.23 mmol) and NaOH (0.627 g, 15.69 mmol) in water (3 mL). The resulting solution was stirred at RT for 3 h. After completion of the reaction (reaction monitored by TLC), solvent was removed under reduced pressure. The RM was diluted with 3 mL of water, cooled to 0° C., then acidified to pH 3 with 1N HCl, and extracted with ethyl acetate (50 mL×2). The organic layer was washed water (50 mL), and saturated brine solution (30 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The product was obtained as white color solid (0.9 g, yield: 97.2%). To a 25 mL RB flask fitted with magnetic stirrer After completion of the reaction (reaction monitored by TLC), solvent was removed under reduced pressure The RM was diluted with 3 mL of water cooled to 0° C. extracted with ethyl acetate (50 mL×2) The organic layer was washed water (50 mL), and saturated brine solution (30 mL) The organic layer was dried over anhydrous Na2SO4 the solvent was removed under reduced pressure

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

Procedure: To a 25 mL RB flask fitted with magnetic stirrer was charged 5 mL of methanol: and 5 mL of THF. To the stirred solvent, was added methyl (1R,2R)-2-(4-aminophenyl)cyclo propane carboxylate (1 g, 5.23 mmol) and NaOH (0.627 g, 15.69 mmol) in water (3 mL). The resulting solution was stirred at RT for 3 h. After completion of the reaction (reaction monitored by TLC), solvent was removed under reduced pressure. The RM was diluted with 3 mL of water, cooled to 0° C., then acidified to pH 3 with 1N HCl, and extracted with ethyl acetate (50 mL×2). The organic layer was washed water (50 mL), and saturated brine solution (30 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The product was obtained as white color solid (0.9 g, yield: 97.2%). To a 25 mL RB flask fitted with magnetic stirrer After completion of the reaction (reaction monitored by TLC), solvent was removed under reduced pressure The RM was diluted with 3 mL of water cooled to 0° C. extracted with ethyl acetate (50 mL×2) The organic layer was washed water (50 mL), and saturated brine solution (30 mL) The organic layer was dried over anhydrous Na2SO4 the solvent was removed under reduced pressure

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

Procedure: To a 1000 mL parr hydrogenater flask with methanol (70 mL) and ethyl acetate (70 mL), was added methyl (1R,2R)-2-(4-nitrophenyl)cyclo propane carboxylate (14 g, 63.3 mmol) and 10% Pd/C (2 g) under N2 atmosphere. The RM was hydrogenated at 40 psi for 5 h. RM was diluted with ethyl acetate (100 mL), filtered through celite bed to remove Pd/C and evaporated to dryness under reduced pressure. The crude was purified by flash column chromatography on silica gel (230/400 mesh), to give the product (4 g, yield: 33.1%). MS (ESI, 120 eV): m/z=192.1 (M+H)+; 1H NMR (300 MHz, CDCl3): δ 6.83-6.86 (d, 2H), 6.58-6.61 (d, 2H), 3.63 (s, 3H), 2.36-2.39 (m, 1H), 1.69-1.75 (m, 1H), 1.42-1.49 (m, 1H), 1.14-1.20 (m, 1H). filtered through celite bed to remove Pd/C evaporated to dryness under reduced pressure The crude was purified by flash column chromatography on silica gel (230/400 mesh)

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

Procedure: Compound 15 was synthesized from methyl (1R,2R)-2-(4-aminophenyl)cyclopropane carboxylate (0.18 g, 0.9 mmol) and 4-{[(2Z)-2-(methoxyimino)-2-(2-methylphenyl)ethyl]oxy}benzaldehyde (0.31 g, 1.1 mmol) by following the procedure described in Scheme 3 (0.12 g, yield: 28%); Purity: 91.26%.

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

Procedure: To a 25 mL RB flask fitted with magnetic stirrer was charged 5 mL of methanol: and 5 mL of THF. To the stirred solvent, was added methyl (1R,2R)-2-(4-aminophenyl)cyclo propane carboxylate (1 g, 5.23 mmol) and NaOH (0.627 g, 15.69 mmol) in water (3 mL). The resulting solution was stirred at RT for 3 h. After completion of the reaction (reaction monitored by TLC), solvent was removed under reduced pressure. The RM was diluted with 3 mL of water, cooled to 0° C., then acidified to pH 3 with 1N HCl, and extracted with ethyl acetate (50 mL×2). The organic layer was washed water (50 mL), and saturated brine solution (30 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The product was obtained as white color solid (0.9 g, yield: 97.2%). To a 25 mL RB flask fitted with magnetic stirrer After completion of the reaction (reaction monitored by TLC), solvent was removed under reduced pressure The RM was diluted with 3 mL of water cooled to 0° C. extracted with ethyl acetate (50 mL×2) The organic layer was washed water (50 mL), and saturated brine solution (30 mL) The organic layer was dried over anhydrous Na2SO4 the solvent was removed under reduced pressure

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

Procedure: To a 1000 mL parr hydrogenater flask with methanol (70 mL) and ethyl acetate (70 mL), was added methyl (1R,2R)-2-(4-nitrophenyl)cyclo propane carboxylate (14 g, 63.3 mmol) and 10% Pd/C (2 g) under N2 atmosphere. The RM was hydrogenated at 40 psi for 5 h. RM was diluted with ethyl acetate (100 mL), filtered through celite bed to remove Pd/C and evaporated to dryness under reduced pressure. The crude was purified by flash column chromatography on silica gel (230/400 mesh), to give the product (4 g, yield: 33.1%). MS (ESI, 120 eV): m/z=192.1 (M+H)+; 1H NMR (300 MHz, CDCl3): δ 6.83-6.86 (d, 2H), 6.58-6.61 (d, 2H), 3.63 (s, 3H), 2.36-2.39 (m, 1H), 1.69-1.75 (m, 1H), 1.42-1.49 (m, 1H), 1.14-1.20 (m, 1H). filtered through celite bed to remove Pd/C evaporated to dryness under reduced pressure The crude was purified by flash column chromatography on silica gel (230/400 mesh)