Sodium bis(trimethylsilyl)amide → HCID 68737330, compound

Temperature

-78 °C

To a stirred solution of 2-oxoindoline-4-carbonitrile (2.97 g, 18.8 mmol; prepared as described in WO 00/21920) in THF (40 mL) was added dropwise a 1.0 M THF solution of NaHMDS (78.2 mL, 78.2 mmol) at about −78° C. under N2. After stirring at about −78° C. for about 30 min, N-benzylbis(2-chloroethyl)amine hydrochloride (4.20 g, 15.6 mmol) was added as a solid. The reaction mixture was stirred at about −78° C. for about 30 minutes and then allowed to warm to rt. The reaction mixture was then heated at reflux for 2 h. After cooling to about 0° C., the reaction was quenched by the addition of saturated aqueous NH4Cl solution. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (DCM:MeOH, 60:1) to give 1′-benzyl-2-oxo spiro[indoline-3,4′-piperidine]-4-carbonitrile (2.10 g, 42%) as a solid. LCMS (APCI+) m/z 318 [M+H]+; Rt=2.42 min.

1. stirringThe reaction mixture was stirred at about −78° C. for about 30 minutes
2. temperatureto warm to rt
3. temperatureThe reaction mixture was then heated
4. temperatureat reflux for 2 h
5. temperatureAfter cooling to about 0° C.
6. customthe reaction was quenched by the addition of saturated aqueous NH4Cl solution
7. customThe reaction mixture was partitioned between EtOAc and water
8. extractionThe aqueous layer was extracted with EtOAc
9. washThe combined organic layers were washed with brine
10. customdried
11. concentrationconcentrated
12. customThe residue was purified by column chromatography (DCM:MeOH, 60:1)

ORD record

ord-d50f7558a50840819f9fb266966407fd

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324221B2