N,N,N',N'-Tetramethylethylenediamine → Spiro[indole-3,4'-oxan]-2(1H)-one

Butyllithium (2.5 M in hexanes, 3.76 mL, 9.39 mmol) was added to a solution of oxindole (500 mg, 3.76 mmol) at −78° C. in THF (40 mL). After complete addition, N,N,N′,N′-tetramethylethane-1,2-diamine (1.48 mL, 9.76 mmol) was added, maintaining the internal temperature <−70° C. After 1 h at −78° C., 2-iodoethyl ether (4.90 g, 15.0 mmol) was added and the reaction warmed to ambient temperature. After 48 h the reaction was quenched with H2O (5 mL) and the mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The aqueous solution was extracted with EtOAc (3×50 mL) and the combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 97:3, gave the title compound. MS: m/z=204 (M+1).

1. additionwas added
2. temperaturemaintaining the internal temperature <−70° C
3. customAfter 48 h the reaction was quenched with H2O (5 mL)
4. customthe mixture was partitioned between EtOAc (100 mL) and H2O (100 mL)
5. extractionThe aqueous solution was extracted with EtOAc (3×50 mL)
6. washthe combined organic layers were washed with brine (20 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification by silica gel chromatography
11. washeluting with a gradient of CH2Cl2

ORD record

ord-0f4efaa020a5402b9af1a371bdd47925

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173655B2