N-[(4-chlorophenyl)methyl]acetamide

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

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

Procedure: N-(4-chlorobenzyl)acetamide (2.337 g, 12.726 mmol) was dissolved in THF (100 ml) and was cooled to zero degrees under argon atmosphere. (Methylthio)methane compound with borane (1:1) (2.417 g, 31.815 mmol) was added and the mixture was refluxed overnight at RT. HCl (15 ml, 10%) was gently added and was stirred overnight. The solvent was removed by evaporation. Diethyl ether (20 ml) was added and the product was extracted to the water phase by K2CO3 (3×15 ml). The aqueous phase was acidified by HCl (10 ml, 10%) and the product was extracted to the organic phase by EtOAc (3×15 ml). The organic phase was dried (MgSO4) and the solvent was removed by evaporation to give 0.938 g of N-(4-chlorobenzyl)-N-ethylamine (yield 43.4%). was cooled to zero degrees under argon atmosphere The solvent was removed by evaporation Diethyl ether (20 ml) was added the product was extracted to the water phase by K2CO3 (3×15 ml) the product was extracted to the organic phase by EtOAc (3×15 ml) The organic phase was dried (MgSO4) the solvent was removed by evaporation

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

Procedure: N-(4-chlorobenzyl)acetamide (2.337 g, 12.726 mmol) was dissolved in THF (100 ml) and was cooled to zero degrees under argon atmosphere. (Methylthio)methane compound with borane (1:1) (2.417 g, 31.815 mmol) was added and the mixture was refluxed overnight at RT. HCl (15 ml, 10%) was gently added and was stirred overnight. The solvent was removed by evaporation. Diethyl ether (20 ml) was added and the product was extracted to the water phase by K2CO3 (3×15 ml). The aqueous phase was acidified by HCl (10 ml, 10%) and the product was extracted to the organic phase by EtOAc (3×15 ml). The organic phase was dried (MgSO4) and the solvent was removed by evaporation to give 0.938 g of N-(4-chlorobenzyl)-N-ethylamine (yield 43.4%). was cooled to zero degrees under argon atmosphere The solvent was removed by evaporation Diethyl ether (20 ml) was added the product was extracted to the water phase by K2CO3 (3×15 ml) the product was extracted to the organic phase by EtOAc (3×15 ml) The organic phase was dried (MgSO4) the solvent was removed by evaporation

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acetic acid (1.321 g, 22.000 mmol) was dissolved in DMF (10 ml), 1-(4-chlorophenyl)methanamine (2.804 g, 19.800 mmol) was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (7.770 g, 24.200 mmol) and N-ethyl-N,N-diisopropylamine (5.971 g, 46.200 mmol) was added. The solution was stirred for two hours at room temperature. EtOAc (20 ml) was added and the organic phase was washed with Na2CO3 (3×20 ml, aq) and HCl (0.5 M, 2×, 10 ml). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The residue was purified by preparative HPLC (the initial mobile phase was isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product-containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation and gave 2.337 g of N-(4-chlorobenzyl)acetamide (yield 57.8%). the organic phase was washed with Na2CO3 (3×20 ml, aq) and HCl (0.5 M, 2×, 10 ml) The organic layer was dried (MgSO4) the solvent was removed by evaporation The residue was purified by preparative HPLC (the initial mobile phase the acetonitrile concentration was increased to 100% a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min) the acetonitrile was removed by evaporation EtOAc (10 ml) was added the organic phase was washed with two portions of brine dried (MgSO4) the solvent was removed by evaporation

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

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

Procedure: N-(4-chlorobenzyl)acetamide (2.337 g, 12.726 mmol) was dissolved in THF (100 ml) and was cooled to zero degrees under argon atmosphere. (Methylthio)methane compound with borane (1:1) (2.417 g, 31.815 mmol) was added and the mixture was refluxed overnight at RT. HCl (15 ml, 10%) was gently added and was stirred overnight. The solvent was removed by evaporation. Diethyl ether (20 ml) was added and the product was extracted to the water phase by K2CO3 (3×15 ml). The aqueous phase was acidified by HCl (10 ml, 10%) and the product was extracted to the organic phase by EtOAc (3×15 ml). The organic phase was dried (MgSO4) and the solvent was removed by evaporation to give 0.938 g of N-(4-chlorobenzyl)-N-ethylamine (yield 43.4%). was cooled to zero degrees under argon atmosphere The solvent was removed by evaporation Diethyl ether (20 ml) was added the product was extracted to the water phase by K2CO3 (3×15 ml) the product was extracted to the organic phase by EtOAc (3×15 ml) The organic phase was dried (MgSO4) the solvent was removed by evaporation

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Acetic acid (1.321 g, 22.000 mmol) was dissolved in DMF (10 ml), 1-(4-chlorophenyl)methanamine (2.804 g, 19.800 mmol) was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (7.770 g, 24.200 mmol) and N-ethyl-N,N-diisopropylamine (5.971 g, 46.200 mmol) was added. The solution was stirred for two hours at room temperature. EtOAc (20 ml) was added and the organic phase was washed with Na2CO3 (3×20 ml, aq) and HCl (0.5 M, 2×, 10 ml). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The residue was purified by preparative HPLC (the initial mobile phase was isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product-containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation and gave 2.337 g of N-(4-chlorobenzyl)acetamide (yield 57.8%). the organic phase was washed with Na2CO3 (3×20 ml, aq) and HCl (0.5 M, 2×, 10 ml) The organic layer was dried (MgSO4) the solvent was removed by evaporation The residue was purified by preparative HPLC (the initial mobile phase the acetonitrile concentration was increased to 100% a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min) the acetonitrile was removed by evaporation EtOAc (10 ml) was added the organic phase was washed with two portions of brine dried (MgSO4) the solvent was removed by evaporation

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