Trimethylsilyl cyanide → HCID 76567906, compound

HRID 1728124Notes

Reaction equation

HRID 1728124 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:35])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28](I)[CH:27]=[CH:26][C:25]=3[O:31][CH2:32][CH2:33][OH:34])[C:5]2=[CH:4][CH:3]=1.C[Si]([C:40]#[N:41])(C)C>C(N(CC)CC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:35])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([C:40]#[N:41])[CH:27]=[CH:26][C:25]=3[O:31][CH2:32][CH2:33][OH:34])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 82115Trimethylsilyl cyanideHCID 76567917HCID 76567917, compound

Product 1

HCID 76567906HCID 76567906, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To a mixture of racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[5-iodo-2-(2-hydroxy-ethoxy)-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.1 g, 0.16 mmol) prepared in Example 190c in triethylamine (0.8 mL) was added trimethylsilyl cyanide (23.8 mg, 0.24 mmol) (Aldrich), Tetrakis(triphenylphosphine)palladium (3.7 mg, Aldrich) sequentially. The reaction mixture was refluxed under nitrogen for 2 h. After cooled to room temperature, the reaction mixture was partitioned between saturated water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by chromatography (EtOAc) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[5-cyano-2-(2-hydroxy-ethoxy)-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 38 mg, 46%).

Workup

  1. temperatureThe reaction mixture was refluxed under nitrogen for 2 h
  2. customthe reaction mixture was partitioned between saturated water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (EtOAc)

Sources & evidence

ORD record
ord-1ca6d8d3f8584037a1f8def27b70846a
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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