N,N,N',N'-Tetramethylethylenediamine → (+/-)-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) dropwise, followed by the dropwise addition of tetramethylethylenediamine (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 dropwise. 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 NH4 CI (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 Na2 SO4, 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. stirringThe reaction solution was stirred at −10 to −20° C. for 2 h and at ambient temperature for 16 h
2. customThe reaction mixture was partitioned between saturated NH4 CI (50 mL) and EtOAc (50 mL)
3. extractionThe aqueous phase was further extracted with EtOAc (2×50 mL)
4. customthe combined organic layers were dried over Na2 SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified by silica gel chromatography
8. washeluting with a gradient of hexane:EtOAc —100:0 to 50:50

ORD record

ord-69d9b85b242a42ffab3843c192e250bf

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071772B2