methyl 3-(benzylamino)-2-methylpropanoate

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

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

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

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl methacrylate (7 mL, 0.067 mol, 1.0 equiv), benzylamine (6 mL, 0.055 mol, 0.8 equiv) in methanol (5 ml) was stirred at 70° C. for 2 days. After evaporation of the volatiles, the crude product was purified by flash chromatography (DCM:MeOH=20:1) to give compound methyl 3-(benzylamino)-2-methylpropanoate 9 g, yield: 65%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.32-7.24 (m, 5H), 3.79 (s, 2H), 3.68 (s, 3H), 2.88-2.85 (m, 1H), 2.71-2.63 (m, 2H), 1.16 (d, 3H). After evaporation of the volatiles the crude product was purified by flash chromatography (DCM:MeOH=20:1)

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl methacrylate (7 mL, 0.067 mol, 1.0 equiv), benzylamine (6 mL, 0.055 mol, 0.8 equiv) in methanol (5 mL) was stirred at 70° C. for 2 days. After evaporation of the volatiles, the crude product was purified by flash chromatography (DCM:MeOH=20:1) to give compound methyl 3-(benzylamino)-2-methylpropanoate 9 g, yield: 65%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.32-7.24 (m, 5H), 3.79 (s, 2H), 3.68 (s, 3H), 2.88-2.85 (m, 1H), 2.71-2.63 (m, 2H), 1.16 (d, 3H). After evaporation of the volatiles the crude product was purified by flash chromatography (DCM:MeOH=20:1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl methacrylate (7 mL, 0.067 mol, 1.0 equiv), benzylamine (6 mL, 0.055 mol, 0.8 equiv) in methanol (5 mL) was stirred at 70° C. for 2 days. After evaporation of the volatiles, the crude product was purified by flash chromatography (DCM:MeOH=20:1) to give compound methyl 3-(benzylamino)-2-methylpropanoate 9 g, yield: 65%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.32-7.24 (m, 5H), 3.79 (s, 2H), 3.68 (s, 3H), 2.88-2.85 (m, 1H), 2.71-2.63 (m, 2H), 1.16 (d, 3H). After evaporation of the volatiles the crude product was purified by flash chromatography (DCM:MeOH=20:1)

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

Procedure: 3-Phenylmethylamino-2-methyl-propanoic acid methyl ester (79 g, 0.38 mole) from Example and ethyl acrylate (54.2 ml, 50.06 g, 0.5 mole) were dissolved in 200 ml of methanol and then heated to reflux overnight. After being cooled, the solution was concentrated under vacuum to remove the excess of solvent and ethyl acrylate to yield the crude N-[2-(methoxycarbonyl)propyl]-N-[2-(ethoxycarbonyl)ethyl]phenylmethylamine (110 g, 95%). heated to reflux overnight After being cooled the solution was concentrated under vacuum to remove the excess of solvent and ethyl acrylate

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

Procedure: Methyl methacrylate (64.2 ml, 60.07 g, 0.6 mole) was added slowly at 0° C. (ice bath) to benzylamine (54.6 ml, 53.6 g, 0.5 mole) in 200 ml of methanol. The reaction solution was heated to reflux overnight. After being cooled, the solution was concentrated under vacuum to remove the excess of methyl methacrylate and methanol. Unreacted benzylamine was removed by heating the residue in a Kugelrohr oven under vacuum to yield the crude 3-phenylmethylamino-2-methyl-propanoic acid methyl ester (79.2 g, 76.41%). The reaction solution was heated to reflux overnight After being cooled the solution was concentrated under vacuum to remove the excess of methyl methacrylate and methanol was removed by heating the residue in a Kugelrohr oven under vacuum

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

Procedure: To a mixture of 2.73 g (0.010 mole) of (rac)-3-benzylamino-2-methyl-propanoic acid methyl ester, 1.84 g (0.010 mole) of 2,4-dichloro-5-nitro-pyrimidine, 50 mL of ethyl acetate and 25 mL of water was added 3.0 g (0.030 mole) of potassium bicarbonate. The mixture was stirred for 3 hours, then diluted with 50 mL of ethyl acetate and 50 mL of water. The layers were separated, and the aqueous layer extracted twice with 100 mL of ethyl acetate. The organic layers were washed with 100 mL of brine, combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-ethyl acetate (100:0-97:3) to give 2.55 g of (rac)-3-[benzyl-(2-chloro-5-nitro-pyrimidin-4-yl)-amino]-2-methyl-propanoic acid methyl ester (IV-42) as pale yellow oil. The layers were separated the aqueous layer extracted twice with 100 mL of ethyl acetate The organic layers were washed with 100 mL of brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with dichloromethane-ethyl acetate (100:0-97:3)

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

Procedure: To a solution of benzylamine (10.7 g, 100 mmol) in methanol (100 mL) was added methyl methacrylate (10 g, 100 mmol). The reaction solution was stirred at room temperature for 12 hours. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:1) to give methyl 3-(benzylamino)-2-methylpropanoate as a light yellow oil (12 g, 57%). The reaction mixture was concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:1)