Ammonia → TERT-BUTYL 5-AMINOOCTAHYDRO-2H-ISOINDOLE-2-CARBOXYLATE

To a solution of tert-butyl 5-oxohexahydro-1H-isoindole-2(3H)-carboxylate (11.97 g, 50 mmol) in EtOH (100 mL) were added a solution of NH3 in MeOH (7 M, 100 mL, 700 mmol) and Ti(OiPr)4 (28.42 g, 100 mmol). After addition, the reaction mixture was stirred at rt overnight and NaBH4 (3.78 g, 100 mmol) was added portionwise, then the resulting mixture was stirred at rt for another 5 h. The reaction was quenched with water (100 mL), stirred at rt for 1 h and filtered. The filter cake was washed with DCM (100 mL×3) and the filtrate was concentrated in vacuo. The residue was dissolved in a mixture of EtOAc (100 mL) and water (100 mL), and extracted with EtOAc (250 mL×3). The combined organic phases were washed with brine (250 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the title compound as brown oil (12.02 g, 100%).

1. additionAfter addition
2. stirringthe resulting mixture was stirred at rt for another 5 h
3. customThe reaction was quenched with water (100 mL)
4. stirringstirred at rt for 1 h
5. filtrationfiltered
6. washThe filter cake was washed with DCM (100 mL×3)
7. concentrationthe filtrate was concentrated in vacuo
8. dissolutionThe residue was dissolved in a mixture of EtOAc (100 mL) and water (100 mL)
9. extractionextracted with EtOAc (250 mL×3)
10. washThe combined organic phases were washed with brine (250 mL)
11. dry with materialdried over anhydrous Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-067b2c93aaea4d43a198603c02c693f1

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403801B2