Hydrogen Peroxide → 1,1-Dimethylethyl octahydro-5-hydroxy-2H-isoindole-2-carboxylate

To a solution of tert-butyl 3a,4,7,7a-tetrahydro-1H-isoindole-2(3H)-carboxylate (48.18 g, 215.8 mmol) in THF (500 mL) was added a solution of BH3-DMS in THF (2 M in THF, 130 mL, 260.0 mmol) dropwise at 0° C. The reaction mixture was warmed slowly to rt and stirred overnight, then cooled down to 0° C. again. Methanol (120 mL) was added dropwise to the above mixture, and followed by a mixture of NaOH aqueous solution (3 M, 75 mL, 225 mmol) and H2O2 (30% in water, 75 mL). The resulting mixture was stirred at 60° C. for 1.5 h, then cooled down to rt, and diluted with Et2O (500 mL) and water (450 mL), then extracted with EtOAc (450 mL×3). The combined organic phases were washed with brine (500 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the title compound as orange oil (49.04 g, 94.2%), which was used in the next step without further purification.

1. temperaturecooled down to 0° C. again
2. stirringThe resulting mixture was stirred at 60° C. for 1.5 h
3. temperaturecooled down to rt
4. extractionextracted with EtOAc (450 mL×3)
5. washThe combined organic phases were washed with brine (500 mL)
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-ccd016b8b64e4819bea44ccffc6029a6

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403801B2