tert-butyl 3-(aminomethyl)-3-hydroxyazetidine-1-carboxylate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl 3-cyano-3-(trimethylsilyloxy)azetidine-1-carboxylate (300 mg, 1.11 mmol) in THF (5 mL) was treated with borane methylsulfide complex (2M in THF, 2 mL) and the mixture was heated at 70° C. for 1 h under nitrogen. Then the mixture was cooled to room temperature and quenched with methanol (5 mL) followed by treatment with ethylenediamine (0.28 mL), this mixture was stirred at 25° C. for 1 h, and then warmed to 55° C. for 1 h. After cooling to room temperature, the reaction mixture was treated with tetrabutylammonium fluoride (1 M in THF, 2 mL, 2 mmol), then stirred at 25° C. for 1 h. The mixture was diluted with 50 mL of water, product extracted with ethyl acetate (3×25 mL), organics combined dried with sodium sulfate, filtered and concentrated to afford tert-butyl 3-(aminomethyl)-3-hydroxyazetidine-1-carboxylate (200 mg, crude) as white solid which was used to next step without further purification. Then the mixture was cooled to room temperature quenched with methanol (5 mL) warmed to 55° C. for 1 h After cooling to room temperature stirred at 25° C. for 1 h extracted with ethyl acetate (3×25 mL) organics combined dried with sodium sulfate filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl 3-cyano-3-(trimethylsilyloxy)azetidine-1-carboxylate (300 mg, 1.11 mmol) in THF (5 mL) was treated with borane methylsulfide complex (2M in THF, 2 mL) and the mixture was heated at 70° C. for 1 h under nitrogen. Then the mixture was cooled to room temperature and quenched with methanol (5 mL) followed by treatment with ethylenediamine (0.28 mL), this mixture was stirred at 25° C. for 1 h, and then warmed to 55° C. for 1 h. After cooling to room temperature, the reaction mixture was treated with tetrabutylammonium fluoride (1 M in THF, 2 mL, 2 mmol), then stirred at 25° C. for 1 h. The mixture was diluted with 50 mL of water, product extracted with ethyl acetate (3×25 mL), organics combined dried with sodium sulfate, filtered and concentrated to afford tert-butyl 3-(aminomethyl)-3-hydroxyazetidine-1-carboxylate (200 mg, crude) as white solid which was used to next step without further purification. Then the mixture was cooled to room temperature quenched with methanol (5 mL) warmed to 55° C. for 1 h After cooling to room temperature stirred at 25° C. for 1 h extracted with ethyl acetate (3×25 mL) organics combined dried with sodium sulfate filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl 3-cyano-3-(trimethylsilyloxy)azetidine-1-carboxylate (300 mg, 1.11 mmol) in THF (5 mL) was treated with borane methylsulfide complex (2M in THF, 2 mL) and the mixture was heated at 70° C. for 1 h under nitrogen. Then the mixture was cooled to room temperature and quenched with methanol (5 mL) followed by treatment with ethylenediamine (0.28 mL), this mixture was stirred at 25° C. for 1 h, and then warmed to 55° C. for 1 h. After cooling to room temperature, the reaction mixture was treated with tetrabutylammonium fluoride (1 M in THF, 2 mL, 2 mmol), then stirred at 25° C. for 1 h. The mixture was diluted with 50 mL of water, product extracted with ethyl acetate (3×25 mL), organics combined dried with sodium sulfate, filtered and concentrated to afford tert-butyl 3-(aminomethyl)-3-hydroxyazetidine-1-carboxylate (200 mg, crude) as white solid which was used to next step without further purification. Then the mixture was cooled to room temperature quenched with methanol (5 mL) warmed to 55° C. for 1 h After cooling to room temperature stirred at 25° C. for 1 h extracted with ethyl acetate (3×25 mL) organics combined dried with sodium sulfate filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl 3-cyano-3-(trimethylsilyloxy)azetidine-1-carboxylate (300 mg, 1.11 mmol) in THF (5 mL) was treated with borane methylsulfide complex (2M in THF, 2 mL) and the mixture was heated at 70° C. for 1 h under nitrogen. Then the mixture was cooled to room temperature and quenched with methanol (5 mL) followed by treatment with ethylenediamine (0.28 mL), this mixture was stirred at 25° C. for 1 h, and then warmed to 55° C. for 1 h. After cooling to room temperature, the reaction mixture was treated with tetrabutylammonium fluoride (1 M in THF, 2 mL, 2 mmol), then stirred at 25° C. for 1 h. The mixture was diluted with 50 mL of water, product extracted with ethyl acetate (3×25 mL), organics combined dried with sodium sulfate, filtered and concentrated to afford tert-butyl 3-(aminomethyl)-3-hydroxyazetidine-1-carboxylate (200 mg, crude) as white solid which was used to next step without further purification. Then the mixture was cooled to room temperature quenched with methanol (5 mL) warmed to 55° C. for 1 h After cooling to room temperature stirred at 25° C. for 1 h extracted with ethyl acetate (3×25 mL) organics combined dried with sodium sulfate filtered concentrated