(3S,5S)-1-benzyl-3,5-dimethylpiperazin-2-one

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chlorobenzoxazole-4-carboxylate (970 mg, 4.58 mmol) and (3S,5S)-1-benzyl-3,5-dimethylpiperazin-2-one (1.00 g, 4.58 mmol) in DMF (20 mL), was stirred in a 35° C. oil bath. After 16 h, the reaction mixture was heated to 55° C. After 3 h, potassium carbonate (630 mg, 4.58 mmol) was added. The reaction mixture was stirred for 2 h at 55° C. and then at ambient temperature for 17 h. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes) gave methyl 2-((2S,6S)-4-benzyl-2,6-dimethyl-3-oxopiperazine-1-yl)benzoxazole-4-carboxylate (1.08 g, 60%). 1H NMR consistent. the reaction mixture was heated to 55° C After 3 h The reaction mixture was stirred for 2 h at 55° C. at ambient temperature for 17 h extracted with EtOAc (2×50 mL) The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL) dried (Na2SO4) concentrated under reduced pressure Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chlorobenzoxazole-4-carboxylate (970 mg, 4.58 mmol) and (3S,5S)-1-benzyl-3,5-dimethylpiperazin-2-one (1.00 g, 4.58 mmol) in DMF (20 mL), was stirred in a 35° C. oil bath. After 16 h, the reaction mixture was heated to 55° C. After 3 h, potassium carbonate (630 mg, 4.58 mmol) was added. The reaction mixture was stirred for 2 h at 55° C. and then at ambient temperature for 17 h. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes) gave methyl 2-((2S,6S)-4-benzyl-2,6-dimethyl-3-oxopiperazine-1-yl)benzoxazole-4-carboxylate (1.08 g, 60%). 1H NMR consistent. the reaction mixture was heated to 55° C After 3 h The reaction mixture was stirred for 2 h at 55° C. at ambient temperature for 17 h extracted with EtOAc (2×50 mL) The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL) dried (Na2SO4) concentrated under reduced pressure Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chlorobenzoxazole-4-carboxylate (970 mg, 4.58 mmol) and (3S,5S)-1-benzyl-3,5-dimethylpiperazin-2-one (1.00 g, 4.58 mmol) in DMF (20 mL), was stirred in a 35° C. oil bath. After 16 h, the reaction mixture was heated to 55° C. After 3 h, potassium carbonate (630 mg, 4.58 mmol) was added. The reaction mixture was stirred for 2 h at 55° C. and then at ambient temperature for 17 h. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes) gave methyl 2-((2S,6S)-4-benzyl-2,6-dimethyl-3-oxopiperazine-1-yl)benzoxazole-4-carboxylate (1.08 g, 60%). 1H NMR consistent. the reaction mixture was heated to 55° C After 3 h The reaction mixture was stirred for 2 h at 55° C. at ambient temperature for 17 h extracted with EtOAc (2×50 mL) The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL) dried (Na2SO4) concentrated under reduced pressure Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-chlorobenzoxazole-4-carboxylate (970 mg, 4.58 mmol) and (3S,5S)-1-benzyl-3,5-dimethylpiperazin-2-one (1.00 g, 4.58 mmol) in DMF (20 mL), was stirred in a 35° C. oil bath. After 16 h, the reaction mixture was heated to 55° C. After 3 h, potassium carbonate (630 mg, 4.58 mmol) was added. The reaction mixture was stirred for 2 h at 55° C. and then at ambient temperature for 17 h. The reaction mixture was diluted with H2O (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes) gave methyl 2-((2S,6S)-4-benzyl-2,6-dimethyl-3-oxopiperazine-1-yl)benzoxazole-4-carboxylate (1.08 g, 60%). 1H NMR consistent. the reaction mixture was heated to 55° C After 3 h The reaction mixture was stirred for 2 h at 55° C. at ambient temperature for 17 h extracted with EtOAc (2×50 mL) The combined organic layers were washed with 0.5 N HCl (25 mL), H2O (25 mL), brine (25 mL) dried (Na2SO4) concentrated under reduced pressure Purification by chromatography (silica gel, 10 to 80% EtOAc in hexanes)