Oxindole → (+/-)-5-Bromo-1,3-dihydrospiro[indene-2,3'-indol]-2'(1'H)-one

Temperature

-78 °C

To a solution of oxindole (363 mg, 2.73 mmol) at −78° C. in THF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) drop wise, followed by the drop wise addition of tetranethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at −78° C., then a solution of 4-bromo-1,2-bis(bromomethyl)benzene [Anderson et al., J. Org. Chem. 1979, 44(9), 1519-1533] (1.87 g, 5.45 mmol) in THF (5 mL) was added drop wise. The reaction solution was stirred at −10 to −20° C. for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NH4Cl (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2×50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 50:50, to give the title compound. MS: m/z=315 (M+1).

1. additionfollowed by the drop wise addition of tetranethylethylenediamine (0.905 mL, 6.00 mmol)
2. stirringThe reaction solution was stirred at −10 to −20° C. for 2 h and at ambient temperature for 16 h
3. customThe reaction mixture was partitioned between saturated NH4Cl (50 mL) and EtOAc (50 mL)
4. extractionThe aqueous phase was further extracted with EtOAc (2×50 mL)
5. dry with materialthe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude product was purified by silica gel chromatography
9. washeluting with a gradient of hexane

ORD record

ord-52a78440039b490a9626028ac656fd60

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07659300B2