Sodium bis(trimethylsilyl)amide → HCID 68737330, compound

HRID 529123Notes

Reaction equation

HRID 529123 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:11]=[C:12]1[CH2:20][C:19]2[C:18]([C:21]#[N:22])=[CH:17][CH:16]=[CH:15][C:14]=2[NH:13]1.Cl.[CH2:24]([N:31]([CH2:35][CH2:36]Cl)[CH2:32][CH2:33]Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1>[CH2:24]([N:31]1[CH2:35][CH2:36][C:20]2([C:19]3[C:18]([C:21]#[N:22])=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]2=[O:11])[CH2:33][CH2:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 2777881N,N-Bis(2-chloroethyl)benzylamine hydrochlorideHCID 22661266HCID 22661266, compound

Product 1

HCID 68737330HCID 68737330, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 1.0M THF solution of NaHMDS (158 mL, 158 mmol) at −78° C. was added dropwise to a stirred solution of 2-oxoindoline-4-carbonitrile (6.0 g, 37.3 mmol) in THF (100 mL) under N2. After stirring at −78° C. for 30 minutes, N-benzylbis(2-chloroethyl)amine hydrochloride (10.9 g, 41.2 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 (2×200 mL). The combined organics layers were washed with brine, dried with MgSO4 and concentrated. The residue was purified by column chromatography (1:1 hexanes:EtOAc to EtOAc to give 1′-benzyl-2-oxospiro{indoline-3,4′-piperidine]-4-carbonitrile (4.90 g, 50%) as a solid. LCMS (APCI+) m/z 318 [M+H]+; Rt=2.41 min.

Workup

  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 (2×200 mL)
  9. washThe combined organics layers were washed with brine
  10. dry with materialdried with MgSO4
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (1:1 hexanes

Sources & evidence

ORD record
ord-8ad4d355f7dd414ea7da7c97bc5c3419
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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