Sodium bis(trimethylsilyl)amide → HCID 68738138, compound

Temperature

-78 °C

A stirred solution of 4-bromoindolin-2-one (13.0 g, 61.3 mmol) in THF (500 mL) was treated by the dropwise addition of a 1.0M THF solution of NaHMDS (306 mL, 306 mmol) at −78° C. under nitrogen. After stirring at −78° C. for 30 minutes, N-benzylbis(2-chloroethyl)amine hydrochloride (18.05 g, 67.4 mmol) was added as a solid. The reaction mixture was stirred at −78° C. for 30 minutes and then allowed to warm to room temperature. The reaction mixture was then heated to reflux for 12 hours. After cooling to 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 (3×200 mL) The combined organics layers were washed with brine, dried with MgSO4 and concentrated under reduced pressure. The resulting solid was triturated with DCM/EtOAc to give 1′-benzyl-4-bromospiro[indoline-3,4′-piperidin]-2-one (19.3 g, 85%) as a solid. LCMS (APCI+) m/z 371/373 [M+H]+; Rt=2.71 min.

1. stirringThe reaction mixture was stirred at −78° C. for 30 minutes
2. temperatureto warm to room temperature
3. temperatureThe reaction mixture was then heated
4. temperatureto reflux for 12 hours
5. temperatureAfter cooling to 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 (3×200 mL) The combined organics layers
9. washwere washed with brine
10. dry with materialdried with MgSO4
11. concentrationconcentrated under reduced pressure
12. customThe resulting solid was triturated with DCM/EtOAc

ORD record

ord-06b43812652f4195bd240f54f12e61f7

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324221B2