N-ALLYLBENZYLAMINE

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:0.00; pressure:0.00; stir:

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

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

Procedure: A solution of N-{[(1,1-dimethylethyl)oxy]carbonyl}-N-(phenylmethyl)glycine (D88, 1.06 g, 4.0 mmol), DIPEA (1.38 ml, 8.0 mmol) and TBTU (1.61 g, 5.0 mmol) in dry DMF (8 ml) was stirred at room temperature for 30 min. Then N-(phenylmethyl)-2-propen-1-amine (D87, 647 mg, 4.4 mmol) was added and stirring was continued for another 2 h. After reaction was completed, ethyl acetate was added and the organic layer was washed with water and brine. The residue was purified via flash chromatography to give the title compound (1.50 g, 95%). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.4-7.2 (m, 10H), 5.8-5.5 (m, 1H), 5.2-5.0 (m, 2H), 4.7-4.3 (m, 4H), 4.1-3.7 (m, 4H), 1.5 (s, 9H); MS: (ES/+) m/z: 295 [M-BOC+], C24H30N2O3 requires 394. After reaction the organic layer was washed with water and brine The residue was purified via flash chromatography

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

Procedure: A solution of N-{[(1,1-dimethylethyl)oxy]carbonyl}-N-(phenylmethyl)glycine (D88, 1.06 g, 4.0 mmol), DIPEA (1.38 ml, 8.0 mmol) and TBTU (1.61 g, 5.0 mmol) in dry DMF (8 ml) was stirred at room temperature for 30 min. Then N-(phenylmethyl)-2-propen-1-amine (D87, 647 mg, 4.4 mmol) was added and stirring was continued for another 2 h. After reaction was completed, ethyl acetate was added and the organic layer was washed with water and brine. The residue was purified via flash chromatography to give the title compound (1.50 g, 95%). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.4-7.2 (m, 10H), 5.8-5.5 (m, 1H), 5.2-5.0 (m, 2H), 4.7-4.3 (m, 4H), 4.1-3.7 (m, 4H), 1.5 (s, 9H); MS: (ES/+) m/z: 295 [M-BOC+], C24H30N2O3 requires 394. After reaction the organic layer was washed with water and brine The residue was purified via flash chromatography

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

Procedure: To a solution of benzylamine (5.7 ml, 52.2 mmol) and sodium iodide (38 mg, 0.25 mmol) in DMSO (30 ml) was added dropwise allyl bromide (2.2 ml, 25.4 mmol) at 0° C. under argon. After stirring for 3 h at room temperature the reaction was complete as shown by TLC (cyclohexanes:ethyl acetate 1:1). Then saturated aqueous sodium bicarbonate solution was added, the product was extracted with diethyl ether (100 ml) and the organic layer was washed with brine. The crude product was purified via flash chromatography to give the title compound (2.1 g, 57%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.4-7.2 (m, 5H), 6.0-5.9 (m, 1H), 5.3-5.1 (m, 2H), 3.8 (s, 2H), 3.3 (d, 2H), 1.5 (bs, 1H). the product was extracted with diethyl ether (100 ml) the organic layer was washed with brine The crude product was purified via flash chromatography

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

Procedure: To a solution of benzylamine (5.7 ml, 52.2 mmol) and sodium iodide (38 mg, 0.25 mmol) in DMSO (30 ml) was added dropwise allyl bromide (2.2 ml, 25.4 mmol) at 0° C. under argon. After stirring for 3 h at room temperature the reaction was complete as shown by TLC (cyclohexanes:ethyl acetate 1:1). Then saturated aqueous sodium bicarbonate solution was added, the product was extracted with diethyl ether (100 ml) and the organic layer was washed with brine. The crude product was purified via flash chromatography to give the title compound (2.1 g, 57%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.4-7.2 (m, 5H), 6.0-5.9 (m, 1H), 5.3-5.1 (m, 2H), 3.8 (s, 2H), 3.3 (d, 2H), 1.5 (bs, 1H). the product was extracted with diethyl ether (100 ml) the organic layer was washed with brine The crude product was purified via flash chromatography

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

Procedure: 587 mg of 2-methylene-succinate 4-methyl ester (4.07 mmol), 781 mg of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (4.07 mmol) and 75 mg of 4-(dimethylamino)pyridine (0.61 mmol) were added to the reaction solution containing 300 mg of allylbenzylamine (2.04 mmol) dissolved in methylene chloride solution (0.5 M) with stirring for 10 hrs at room temperature. After the resulting mixture was washed with 5% HCl solution (10 ml), the mixture was diluted with ethyl acetate, washed with 10 ml of solution mixture mixed with saturated NaHCO3 solution and saturated NaCl solution to separate into an organic layer and water layer. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resultant was purified by Silica gel column chromatography with a solvent mixture mixed with EtOAc and hexanes (1:1) as an eluant to give 272 mg of 3-(allyl-benzyl-carbamoyl)-but-3-enoic acid methyl ester (o) (yield: 49%). After the resulting mixture was washed with 5% HCl solution (10 ml) the mixture was diluted with ethyl acetate washed with 10 ml of solution mixture mixed with saturated NaHCO3 solution and saturated NaCl solution to separate into an organic layer and water layer The organic layer was dried over anhydrous MgSO4 filtered concentrated in vacuo The resultant was purified by Silica gel column chromatography with a solvent mixture mixed with EtOAc and hexanes (1:1) as an eluant

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

Procedure: 587 mg of 2-methylene-succinate 4-methyl ester (4.07 mmol), 781 mg of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (4.07 mmol) and 75 mg of 4-(dimethylamino)pyridine (0.61 mmol) were added to the reaction solution containing 300 mg of allylbenzylamine (2.04 mmol) dissolved in methylene chloride solution (0.5 M) with stirring for 10 hrs at room temperature. After the resulting mixture was washed with 5% HCl solution (10 ml), the mixture was diluted with ethyl acetate, washed with 10 ml of solution mixture mixed with saturated NaHCO3 solution and saturated NaCl solution to separate into an organic layer and water layer. The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resultant was purified by Silica gel column chromatography with a solvent mixture mixed with EtOAc and hexanes (1:1) as an eluant to give 272 mg of 3-(allyl-benzyl-carbamoyl)-but-3-enoic acid methyl ester (o) (yield: 49%). After the resulting mixture was washed with 5% HCl solution (10 ml) the mixture was diluted with ethyl acetate washed with 10 ml of solution mixture mixed with saturated NaHCO3 solution and saturated NaCl solution to separate into an organic layer and water layer The organic layer was dried over anhydrous MgSO4 filtered concentrated in vacuo The resultant was purified by Silica gel column chromatography with a solvent mixture mixed with EtOAc and hexanes (1:1) as an eluant