Tetrabutylammonium Fluoride → tert-Butyl 3-(aminomethyl)-3-hydroxyazetidine-1-carboxylate

Temperature

70 °C

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.

1. temperatureThen the mixture was cooled to room temperature
2. customquenched with methanol (5 mL)
3. temperaturewarmed to 55° C. for 1 h
4. temperatureAfter cooling to room temperature
5. stirringstirred at 25° C. for 1 h
6. extractionextracted with ethyl acetate (3×25 mL)
7. dry with materialorganics combined dried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-702635df1bac4e938f16979c676a0110

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2