tert-butyl 3,6-diazabicyclo[3.1.1]heptane-6-carboxylate

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

Procedure: To a solution of 6-(tert-butoxycarbonyl)-3,6-diazabicyclo[3.1.1]heptane (2) (50 mg, 0.25 mmol) in 5 mL of methylene chloride was added triethylamine (67 μL, 0.5 mmol) and the solution was cooled to 0° C. Methoxyethyl chloroformate (32 μL, 27.5 mmol) was added and the solution was stirred for 1 h. The solvent was removed in vacuo and the residue was washed with 50 mM sodium acetate in methylene chloride solution. The solution was stirred 10 min and passed through a phase separator. The solvent was removed in vacuo to give crude 3-(methoxyethoxycarbonyl)-6-(tert-butoxycarbonyl)-3,6-diazabicyclo[3.1.1]heptane. The solvent was removed in vacuo the residue was washed with 50 mM sodium acetate in methylene chloride solution The solution was stirred 10 min The solvent was removed in vacuo

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

Procedure: To a solution of 6-(tert-butoxycarbonyl)-3,6-diazabicyclo[3.1.1]heptane (2) (50 mg, 0.25 mmol) in 5 mL of methylene chloride was added triethylamine (67 μL, 0.5 mmol) and the solution was cooled to 0° C. Propyl chloroformate (31 μL, 27.5 mmol) was added and the solution was stirred for 1 h. The solvent was removed in vacuo and the residue was washed with 50 mM sodium acetate in methylene chloride solution. The solution was stirred 10 min and passed through a phase separator. The solvent was removed in vacuo to give crude 3-(propoxycarbonyl)-6-(tert-butoxycarbonyl)-3,6-diazabicyclo[3.1.1]heptane. The solvent was removed in vacuo the residue was washed with 50 mM sodium acetate in methylene chloride solution The solution was stirred 10 min The solvent was removed in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 48 mL sealed tube were placed 1-bromo-4-iodobenzene (1498.3 mg, 5.30 mmol), tert-butyl 3,6-diazabicyclo[3.1.1]heptane-6-carboxylate (1000.0 mg, 5.04 mmol), Pd2(dba)3 (138.6 mg, 0.15 mmol), XantPhos (262.7 mg, 0.45 mmol), and sodium t-butoxide (1454.2 mg, 15.13 mmol) in toluene (36 ml). The reaction mixture was stirred at 60° C. for 3 h. Then it was cooled to room temperature. Then it was quenched with water and the organic layers were extracted with EtOAc (3×10 mL). The combined organic layers were washed with water (2×10 mL) and brine (1×10 mL), dried (Na2SO4), concentrated, and purified by flash chromatography (100% Hexane to 100% EtOAc) to give 500.0 mg (28%) of tert-butyl 3-(4-bromophenyl)-3,6-diazabicyclo[3.1.1]heptane-6-carboxylate. In a 48 mL sealed tube Then it was cooled to room temperature Then it was quenched with water the organic layers were extracted with EtOAc (3×10 mL) The combined organic layers were washed with water (2×10 mL) and brine (1×10 mL) dried (Na2SO4) concentrated purified by flash chromatography (100% Hexane to 100% EtOAc)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 48 mL sealed tube were placed 1-bromo-4-iodobenzene (1498.3 mg, 5.30 mmol), tert-butyl 3,6-diazabicyclo[3.1.1]heptane-6-carboxylate (1000.0 mg, 5.04 mmol), Pd2(dba)3 (138.6 mg, 0.15 mmol), XantPhos (262.7 mg, 0.45 mmol), and sodium t-butoxide (1454.2 mg, 15.13 mmol) in toluene (36 ml). The reaction mixture was stirred at 60° C. for 3 h. Then it was cooled to room temperature. Then it was quenched with water and the organic layers were extracted with EtOAc (3×10 mL). The combined organic layers were washed with water (2×10 mL) and brine (1×10 mL), dried (Na2SO4), concentrated, and purified by flash chromatography (100% Hexane to 100% EtOAc) to give 500.0 mg (28%) of tert-butyl 3-(4-bromophenyl)-3,6-diazabicyclo[3.1.1]heptane-6-carboxylate. In a 48 mL sealed tube Then it was cooled to room temperature Then it was quenched with water the organic layers were extracted with EtOAc (3×10 mL) The combined organic layers were washed with water (2×10 mL) and brine (1×10 mL) dried (Na2SO4) concentrated purified by flash chromatography (100% Hexane to 100% EtOAc)