Isobutyronitrile → HCID 66743323, compound

HRID 449719Notes

Reaction equation

HRID 449719 reaction equation
F[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[C:8](=[O:13])[NH:7][CH2:6][CH2:5]2.[C:14](#[N:18])[CH:15]([CH3:17])[CH3:16].C[Si]([N-][Si](C)(C)C)(C)C.[K+]>O1CCCC1>[F:12][C:10]1[CH:11]=[C:2]([C:15]([CH3:17])([CH3:16])[C:14]#[N:18])[CH:3]=[C:4]2[C:9]=1[C:8](=[O:13])[NH:7][CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 6559IsobutyronitrileHCID 3251421Potassium bis(trimethylsilyl)amide2×HCID 667426241352398-60-7

Product 1

HCID 66743323HCID 66743323, compoundYield 6.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a flask containing a solution of 6,8-difluoro-3,4-dihydro-2H-isoquinolin-1-one (4 g, 21.8 mmol) and isobutyronitrile (6.04 g, 87.4 mmol) in dry tetrahydrofuran (45 ml) was added a solution of potassium bis(trimethylsily)amide (50.4 ml, 0.91M in tetrahydrofuran) and the mixture was placed in an oil bath and heated to 70° C. On heating a red-brown homogeneous solution was obtained within 5 minutes. After 1 hour at 70° C., additional potassium bis(trimethylsily)amide (5 ml of 0.91 M) was added and was stirring continued for another 30 minutes. The flask was cooled to ambient temperature and the reaction was quenched with water (125 ml). Ethyl acetate (100 ml) was added and the material was transferred to a separatory funnel. The organic phase was collected and the aqueous phase was back extracted with ethyl acetate (2×70 ml). The combined organic phases were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 100% dichloromethane to 3% methanol/dichloromethane to provide a semi-pure component (710 mg, 33% purity) as well as pure product as a white powder (316 mg). (M+H)+=233 m/e.

Workup

  1. customthe mixture was placed in an oil bath
  2. temperatureOn heating a red-brown homogeneous solution
  3. customwas obtained within 5 minutes
  4. waitcontinued for another 30 minutes
  5. temperatureThe flask was cooled to ambient temperature
  6. customthe reaction was quenched with water (125 ml)
  7. additionEthyl acetate (100 ml) was added
  8. customthe material was transferred to a separatory funnel
  9. customThe organic phase was collected
  10. extractionthe aqueous phase was back extracted with ethyl acetate (2×70 ml)
  11. dry with materialThe combined organic phases were dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by chromatography on silica gel eluting with 100% dichloromethane to 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-cf2501186d6949898f5eb957b733e7ec
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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