Sodium borohydride → Ethyl {4-[9-(ethyloxy)-4-hydroxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-3-fluorophenyl}acetate

To a solution of ethyl {4-[4-(ethyloxy)-9-hydroxy-1,3-dioxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-3-fluorophenyl}acetate (2.50 g, 5.72 mmol) in THF (50 ml) under an argon atmosphere, was added sodium borohydride (0.217 g, 5.72 mmol) followed by borane THF complex solution (1.0M in THF, 5.72 ml, 5.72 mmol). This was stirred at room temperature for 2 hours. A further 5.72 mmol of sodium borohydride and borane THF complex was added to the reaction mixture and stirring continued for 2 hours. Finally, a further 2.86 mmol addition of sodium borohydride and borane THF complex was made and stirring continued for 1.5 hours until the reaction was complete. This was quenched with ethyl acetate (100 ml) and methanol (3 ml) then washed with 2N HCl (100 ml). The aqueous was re-extracted with ethyl acetate (200 ml). The combined organics were washed with brine (200 ml), dried over magnesium sulphate, filtered and evaporated to give the title compound as a pale yellow solid (2.45 g, 5.79 mmol).

1. stirringstirring
2. waitcontinued for 2 hours
3. stirringstirring
4. waitcontinued for 1.5 hours until the reaction
5. customThis was quenched with ethyl acetate (100 ml) and methanol (3 ml)
6. washthen washed with 2N HCl (100 ml)
7. extractionThe aqueous was re-extracted with ethyl acetate (200 ml)
8. washThe combined organics were washed with brine (200 ml)
9. dry with materialdried over magnesium sulphate
10. filtrationfiltered
11. customevaporated

ORD record

ord-c92bf9c790674d8db3865294738c3db8

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207213B2