Ammonia → 8-AMino-2-Boc-2-azaspiro[4.5]decane

To a solution of tert-butyl 5-oxohexahydro-1H-isoindole-2(3H)-carboxylate (9.20 g, 36.31 mmol) in EtOH (290 mL) were added a solution of NH3 in MeOH (7 M, 290 mL, 2030 mmol) and Ti(Oi-Pr)4 (20.64 g, 72.62 mmol). After addition, the reaction mixture was stirred at rt for 6 h and NaBH4 (2.06 g, 54.47 mmol) was added portionwise. After addition, the resulting mixture was stirred at rt for 2 h, quenched with saturated ammonium hydroxide aqueous solution (150 mL), stirred at rt for 15 min and filtered. The filter cake was washed with DCM (150 mL) and the filtrate was concentrated in vacuo. The residue was dissolved in DCM (200 mL) and extracted with water (150 mL×2). The organic phase was washed with brine (100 mL), dried over anhydrous Na2SO4, concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/1) to give the product as yellow oil (7.34 g, 79.5%).

1. additionAfter addition
2. additionAfter addition
3. stirringthe resulting mixture was stirred at rt for 2 h
4. customquenched with saturated ammonium hydroxide aqueous solution (150 mL)
5. stirringstirred at rt for 15 min
6. filtrationfiltered
7. washThe filter cake was washed with DCM (150 mL)
8. concentrationthe filtrate was concentrated in vacuo
9. dissolutionThe residue was dissolved in DCM (200 mL)
10. extractionextracted with water (150 mL×2)
11. washThe organic phase was washed with brine (100 mL)
12. dry with materialdried over anhydrous Na2SO4
13. concentrationconcentrated in vacuo
14. customThe residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/1)

ORD record

ord-cd92497ffd0e4c45a46b4d188cd1a751

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403801B2