(Dimethyl sulfide)trihydroboron → 4-bromo-2,3-dihydro-1H-isoindole

Temperature

0 °C

To a solution of 4-bromoisoindolin-1-one (4 mmol) in THF (8 mL) was added borane-dimethyl sulfide complex (2M in THF, 14 mL) at 0° C. The reaction mixture was allowed to stir at reflux overnight and was then cooled to 0° C. The reaction mixture was quenched by the slow addition of MeOH (2 mL) and then 3N HCl. The reaction mixture was allowed to stir at reflux for 3 hr and then concentrated. Water was added to the residue and the pH of the solution was adjusted to >9 with 4N NaOH. The solution was extracted with diethyl ether. The organic solutions from this basic extraction were combined, dried over Na2SO4, filtered and concentrated to give 4-bromoisoindoline, which was dissolved in THF (5 mL). To this solution was added potassium carbonate (4 mmol) in water (0.5 mL), and BOC2O (2 mmol). The reaction mixture was allowed to stir at rt overnight. The reaction mixture was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 4-bromo-1,3-dihydro-2H-isoindole-2-carboxylate (0.8 mmol, 20%).

1. temperatureat reflux overnight
2. customThe reaction mixture was quenched by the slow addition of MeOH (2 mL)
3. stirringto stir
4. temperatureat reflux for 3 hr
5. concentrationconcentrated
6. additionWater was added to the residue
7. extractionThe solution was extracted with diethyl ether
8. extractionThe organic solutions from this basic extraction
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-2ca3e24e99a44bcab4dccd13b40607cc

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07795249B2