Borane;tetrahydrofuran → Benzyl 4-amino-3,3-dimethylpyrrolidine-1-carboxylate

Temperature

50 °C

To a solution of phenylmethyl (4Z)-3,3-dimethyl-4-[(methyloxy)imino]-1-pyrrolidinecarboxylate (0.7126 g, 2.579 mmol) in THF (26 mL) was added borane-THF complex (1.0 M in THF, 5.2 mL, 5.2 mmol). The solution was heated at 50° C. and stirred for 2 h. The solution was then cooled to room temperature and quenched by addition of 6 N aq. NaOH (2 mL). The mixture was diluted with brine and extracted with Et2O (3×100 mL). The combined organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. To a solution of the residue in MeOH (20 mL) was added 50% aq. NH2OH (5 mL), and the solution was heated at 60° C. and stirred overnight. The solution was then cooled to room temperature and concentrated in vacuo. The residue was partitioned between DCM (200 mL) and 1 N aq. NaOH (50 mL), and the organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give racemic phenylmethyl 4-amino-3,3-dimethyl-1-pyrrolidinecarboxylate (0.5899 g, 92% yield) as a colorless oil. LCMS: (M+H)+: 249.1.

1. temperatureThe solution was then cooled to room temperature
2. customquenched by addition of 6 N aq. NaOH (2 mL)
3. additionThe mixture was diluted with brine
4. extractionextracted with Et2O (3×100 mL)
5. dry with materialThe combined organic phase was dried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. additionTo a solution of the residue in MeOH (20 mL) was added 50% aq. NH2OH (5 mL)
9. temperaturethe solution was heated at 60° C.
10. stirringstirred overnight
11. temperatureThe solution was then cooled to room temperature
12. concentrationconcentrated in vacuo
13. customThe residue was partitioned between DCM (200 mL) and 1 N aq. NaOH (50 mL)
14. dry with materialthe organic phase was dried over anhydrous MgSO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo

ORD record

ord-b6c1ec6ca3ac48828c53764164391796

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893056B2