methyl 4-[[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]benzoate

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

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

Procedure: To 12.2 g of the compound obtained in step (1-2) above was added 20 ml of an ethyl acetate solution of 4N hydrochloric acid under ice-cooling and after stirring the mixture for one hour, the crystals formed were collected by filtration to provide 6.8 g (yield 90%) of 4-(N-methylaminomethyl)benzoic acid methyl ester hydrochloride. Then, 6.5 g of the crystals thus obtained was dissolved in 30 ml of DMF and 4.2 ml of triethylamine and 5.0 g of (S)-2-methylbutyl bromide were added to the solution under ice-cooling. Then, 1.3 g of 60% sodium hydride was added little by little to the solution and the mixture was heated to 80° C. for from 1 to 2 hours. After cooling, the reaction mixture was diluted with 80 ml of diethyl ether and 5 ml of purified water was added dropwise slowly to the solution. The organic layer formed was collected and, after successively being washed with 20 ml of purified water, 20 ml of a saturated aqueous sodium hydrogen carbonate solution, and then 20 ml of a saturated aqueous sodium chloride solution, dried with magnesium sulfate, and then the solvent was distilled off under reduced pressure. cooling the crystals formed were collected by filtration

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

Procedure: To 12.2 g of the compound obtained in step (1-2) above was added 20 ml of an ethyl acetate solution of 4N hydrochloric acid under ice-cooling and after stirring the mixture for one hour, the crystals formed were collected by filtration to provide 6.8 g (yield 90%) of 4-(N-methylaminomethyl)benzoic acid methyl ester hydrochloride. Then, 6.5 g of the crystals thus obtained was dissolved in 30 ml of DMF and 4.2 ml of triethylamine and 5.0 g of (S)-2-methylbutyl bromide were added to the solution under ice-cooling. Then, 1.3 g of 60% sodium hydride was added little by little to the solution and the mixture was heated to 80° C. for from 1 to 2 hours. After cooling, the reaction mixture was diluted with 80 ml of diethyl ether and 5 ml of purified water was added dropwise slowly to the solution. The organic layer formed was collected and, after successively being washed with 20 ml of purified water, 20 ml of a saturated aqueous sodium hydrogen carbonate solution, and then 20 ml of a saturated aqueous sodium chloride solution, dried with magnesium sulfate, and then the solvent was distilled off under reduced pressure. cooling the crystals formed were collected by filtration

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

Procedure: To a solution of methyl 4-[[(tert-butoxycarbonyl)amino]methyl]benzoate (compound obtained in Reference Example 81(1), 2.0 g) in tetrahydrofuran (20 mL) is added sodium hydride (60% dispersion in mineral oil, 0.9 g) under ice-cooling. The mixture is stirred at room temperature for 30 minutes and then to the reaction mixture is added dropwise methyl iodide (2.3 mL). The mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with ethyl acetate, washed with water, and concentrated in vacuo to give methyl 4-[[N-methyl-N-(tert-butoxycarbonyl)amino]-methyl]benzoate (1.9 g, yield; 94%) as a yellow oil. MS (APCI) m/z: 280 [M+H]+ cooling The mixture is stirred at room temperature for 3 hours washed with water concentrated in vacuo

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

Procedure: To a solution of methyl 4-[[(tert-butoxycarbonyl)amino]methyl]benzoate (compound obtained in Reference Example 81(1), 2.0 g) in tetrahydrofuran (20 mL) is added sodium hydride (60% dispersion in mineral oil, 0.9 g) under ice-cooling. The mixture is stirred at room temperature for 30 minutes and then to the reaction mixture is added dropwise methyl iodide (2.3 mL). The mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with ethyl acetate, washed with water, and concentrated in vacuo to give methyl 4-[[N-methyl-N-(tert-butoxycarbonyl)amino]-methyl]benzoate (1.9 g, yield; 94%) as a yellow oil. MS (APCI) m/z: 280 [M+H]+ cooling The mixture is stirred at room temperature for 3 hours washed with water concentrated in vacuo

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

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

Procedure: To 12.2 g of the compound obtained in step (1-2) above was added 20 ml of an ethyl acetate solution of 4N hydrochloric acid under ice-cooling and after stirring the mixture for one hour, the crystals formed were collected by filtration to provide 6.8 g (yield 90%) of 4-(N-methylaminomethyl)benzoic acid methyl ester hydrochloride. Then, 6.5 g of the crystals thus obtained was dissolved in 30 ml of DMF and 4.2 ml of triethylamine and 5.0 g of (S)-2-methylbutyl bromide were added to the solution under ice-cooling. Then, 1.3 g of 60% sodium hydride was added little by little to the solution and the mixture was heated to 80° C. for from 1 to 2 hours. After cooling, the reaction mixture was diluted with 80 ml of diethyl ether and 5 ml of purified water was added dropwise slowly to the solution. The organic layer formed was collected and, after successively being washed with 20 ml of purified water, 20 ml of a saturated aqueous sodium hydrogen carbonate solution, and then 20 ml of a saturated aqueous sodium chloride solution, dried with magnesium sulfate, and then the solvent was distilled off under reduced pressure. cooling the crystals formed were collected by filtration

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

Procedure: To a solution of methyl 4-[[(tert-butoxycarbonyl)amino]methyl]benzoate (compound obtained in Reference Example 81(1), 2.0 g) in tetrahydrofuran (20 mL) is added sodium hydride (60% dispersion in mineral oil, 0.9 g) under ice-cooling. The mixture is stirred at room temperature for 30 minutes and then to the reaction mixture is added dropwise methyl iodide (2.3 mL). The mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with ethyl acetate, washed with water, and concentrated in vacuo to give methyl 4-[[N-methyl-N-(tert-butoxycarbonyl)amino]-methyl]benzoate (1.9 g, yield; 94%) as a yellow oil. MS (APCI) m/z: 280 [M+H]+ cooling The mixture is stirred at room temperature for 3 hours washed with water concentrated in vacuo