iodocyclobutane

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

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

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: LHMDS (1 M solution in THF, 2.4 mL, 2.4 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (494 mg, 2 mmol) in THF (5 mL). Stirred at −50° C. for 5 min then warmed to 0° C. and stirred for 5 min. After cooling back to −50° C., iodocyclobutane (736 mg, 4 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (10 mL) was added, extracted with EtOAc (3×25 mL). The combined organic layer was washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated to give crude product 3-cyclobutyl-1-(2,6-dimethyl-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester which was taken on directly to the next step. MS: (ES) m/z 302.3 (M+H+). then warmed to 0° C. stirred for 5 min After cooling back to −50° C. the resulting reaction mixture was warmed to room temperature stirred for 2 h extracted with EtOAc (3×25 mL) The combined organic layer was washed with water (50 mL), brine (50 mL) dried (Na2SO4) evaporated

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: LHMDS (1 M solution in THF, 2.4 mL, 2.4 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (494 mg, 2 mmol) in THF (5 mL). Stirred at −50° C. for 5 min then warmed to 0° C. and stirred for 5 min. After cooling back to −50° C., iodocyclobutane (736 mg, 4 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (10 mL) was added, extracted with EtOAc (3×25 mL). The combined organic layer was washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated to give crude product 3-cyclobutyl-1-(2,6-dimethyl-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester which was taken on directly to the next step. MS: (ES) m/z 302.3 (M+H+). then warmed to 0° C. stirred for 5 min After cooling back to −50° C. the resulting reaction mixture was warmed to room temperature stirred for 2 h extracted with EtOAc (3×25 mL) The combined organic layer was washed with water (50 mL), brine (50 mL) dried (Na2SO4) evaporated

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: LHMDS (1 M solution in THF, 2.4 mL, 2.4 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (494 mg, 2 mmol) in THF (5 mL). Stirred at −50° C. for 5 min then warmed to 0° C. and stirred for 5 min. After cooling back to −50° C., iodocyclobutane (736 mg, 4 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (10 mL) was added, extracted with EtOAc (3×25 mL). The combined organic layer was washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated to give crude product 3-cyclobutyl-1-(2,6-dimethyl-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester which was taken on directly to the next step. MS: (ES) m/z 302.3 (M+H+). then warmed to 0° C. stirred for 5 min After cooling back to −50° C. the resulting reaction mixture was warmed to room temperature stirred for 2 h extracted with EtOAc (3×25 mL) The combined organic layer was washed with water (50 mL), brine (50 mL) dried (Na2SO4) evaporated

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: LHMDS (1 M solution in THF, 2.4 mL, 2.4 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (494 mg, 2 mmol) in THF (5 mL). Stirred at −50° C. for 5 min then warmed to 0° C. and stirred for 5 min. After cooling back to −50° C., iodocyclobutane (736 mg, 4 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (10 mL) was added, extracted with EtOAc (3×25 mL). The combined organic layer was washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated to give crude product 3-cyclobutyl-1-(2,6-dimethyl-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester which was taken on directly to the next step. MS: (ES) m/z 302.3 (M+H+). then warmed to 0° C. stirred for 5 min After cooling back to −50° C. the resulting reaction mixture was warmed to room temperature stirred for 2 h extracted with EtOAc (3×25 mL) The combined organic layer was washed with water (50 mL), brine (50 mL) dried (Na2SO4) evaporated