1,1-Dimethylethyl octahydro-5-hydroxy-2H-isoindole-2-carboxylate → 2-Boc-5-oxo-octahydro-isoindole

Temperature

0 °C

To a solution of tert-butyl 5-hydroxyhexahydro-1H-isoindole-2(3H)-carboxylate (48.98 g, 203.0 mmol) in DCM (500 mL) at 0° C. was added DMP (103.31 g, 243.6 mmol) portionwise. After addition, the reaction mixture was stirred at 0° C. for 0.5 h and then moved to rt overnight, cooled down to 0° C. and washed with a mixture of NaHCO3/Na2S2O3 saturated solution (v/v, 1/1, 500 mL), then stirred at 0° C. for 0.5 h and filtered. The filter cake was washed with DCM (250 mL×3) and the filtrate was extracted with DCM (250 mL×3). The combined organic phases were washed with brine (500 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5) to give the title compound as yellow oil (48.58 g, 100%).

1. additionAfter addition
2. waitmoved to rt overnight
3. temperaturecooled down to 0° C.
4. washwashed with a mixture of NaHCO3/Na2S2O3 saturated solution (v/v, 1/1, 500 mL)
5. stirringstirred at 0° C. for 0.5 h
6. filtrationfiltered
7. washThe filter cake was washed with DCM (250 mL×3)
8. extractionthe filtrate was extracted with DCM (250 mL×3)
9. washThe combined organic phases were washed with brine (500 mL)
10. dry with materialdried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5)

ORD record

ord-2db61de3efac4ab4b9e212c53e89ecd4

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403801B2