tert-butyl 2-methyl-3-oxoazetidine-1-carboxylate

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

Procedure: To a mixture of 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester (crude, 1.17 mmol) in MeOH (5 mL) and AcOH (0.5 mL) was added 6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #2, Step E, 0.050 g, 0.215 mmol). The reaction mixture was stirred at ambient temperature for 0.5 h then NaBH3CN (0.068 g, 1.076 mmol) was added. The mixture was stirred at ambient temperature overnight then concentrated in vacuo. The residue was purified by preparative HPLC (Table 3, Method 24) to give 2-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (0.016 g, 18%). LC/MS (Table 1, Method 5) Rt=1.087 min; MS m/z: 424 [M+23]+. The mixture was stirred at ambient temperature overnight then concentrated in vacuo The residue was purified by preparative HPLC (Table 3, Method 24)

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

Procedure: To a mixture of 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester (crude, 1.17 mmol) in MeOH (5 mL) and AcOH (0.5 mL) was added 6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #2, Step E, 0.050 g, 0.215 mmol). The reaction mixture was stirred at ambient temperature for 0.5 h then NaBH3CN (0.068 g, 1.076 mmol) was added. The mixture was stirred at ambient temperature overnight then concentrated in vacuo. The residue was purified by preparative HPLC (Table 3, Method 24) to give 2-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (0.016 g, 18%). LC/MS (Table 1, Method 5) Rt=1.087 min; MS m/z: 424 [M+23]+. The mixture was stirred at ambient temperature overnight then concentrated in vacuo The residue was purified by preparative HPLC (Table 3, Method 24)

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

Procedure: (3-Diazo-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester (0.250 g, 1.17 mmol) was dissolved in anhydrous DCM (6 mL) and Et3N (1.18 mg, 0.012 mmol) was added. The reaction mixture was cooled to 0° C. and rhodium (II) acetate (0.010 g, 0.023 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h then concentrated in vacuo to give 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester, which was used in the next step without further purification. TLC (eluting with 20% EtOAc/heptane) Rf=0.3. then concentrated in vacuo

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

Procedure: (3-Diazo-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester (0.250 g, 1.17 mmol) was dissolved in anhydrous DCM (6 mL) and Et3N (1.18 mg, 0.012 mmol) was added. The reaction mixture was cooled to 0° C. and rhodium (II) acetate (0.010 g, 0.023 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h then concentrated in vacuo to give 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester, which was used in the next step without further purification. TLC (eluting with 20% EtOAc/heptane) Rf=0.3. then concentrated in vacuo

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

Procedure: To a mixture of 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester (crude, 1.17 mmol) in MeOH (5 mL) and AcOH (0.5 mL) was added 6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #2, Step E, 0.050 g, 0.215 mmol). The reaction mixture was stirred at ambient temperature for 0.5 h then NaBH3CN (0.068 g, 1.076 mmol) was added. The mixture was stirred at ambient temperature overnight then concentrated in vacuo. The residue was purified by preparative HPLC (Table 3, Method 24) to give 2-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (0.016 g, 18%). LC/MS (Table 1, Method 5) Rt=1.087 min; MS m/z: 424 [M+23]+. The mixture was stirred at ambient temperature overnight then concentrated in vacuo The residue was purified by preparative HPLC (Table 3, Method 24)

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

Procedure: (3-Diazo-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester (0.250 g, 1.17 mmol) was dissolved in anhydrous DCM (6 mL) and Et3N (1.18 mg, 0.012 mmol) was added. The reaction mixture was cooled to 0° C. and rhodium (II) acetate (0.010 g, 0.023 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h then concentrated in vacuo to give 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester, which was used in the next step without further purification. TLC (eluting with 20% EtOAc/heptane) Rf=0.3. then concentrated in vacuo