Potassium Cyanide → HCID 86672016, compound

HRID 473831Notes

Reaction equation

HRID 473831 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:14][C@@H:13](OS(C)(=O)=O)[CH2:12][CH2:11][N:10]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:5]=[CH:6][C:7]=1[F:8].[C-:27]#[N:28].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:27]([C@@H:13]1[CH2:12][CH2:11][N:10]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@@H:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)[CH2:14]1)#[N:28]

Participants

5

Reactant 2

HCID 9032Potassium CyanideHCID 86672014HCID 86672014, compound

Product 1

HCID 86672016HCID 86672016, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (±)-1,1-dimethylethyl (2R,4S)-2-(3,4-difluorophenyl)-4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (0.72 g, 1.8 mmol), and potassium cyanide (0.33 g, 3.7 mmol) in N,N-dimethylformamide (3.3 mL) was stirred at 90° C. for 18 hours. The reaction mixture was cooled, diluted with ethyl acetate (50 mL), washed twice with 5% lithium chloride solution (30 mL), then brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (5% to 25% ethyl acetate in hexanes gradient) to give (±)-1,1-dimethylethyl (2R,4R)-4-cyano-2-(3,4-difluorophenyl)piperidine-1-carboxylate (165 mg, 30% yield). MS (EI) for C17H23F2N2O2: 323 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed twice with 5% lithium chloride solution (30 mL)
  3. dry with materialbrine, dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (5% to 25% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-7afb76f7cf0a4fae8ddb87dcd305305e
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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