Isobutyronitrile → HCID 66742829, compound

HRID 449579Notes

Reaction equation

HRID 449579 reaction equation
[F:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[C:4]([CH3:9])[C:3]=1[C:10]1[O:11][CH2:12][C:13]([CH3:16])([CH3:15])[N:14]=1.[C:17](#[N:21])[CH:18]([CH3:20])[CH3:19].C(#N)C.C(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>O1CCCC1>[CH3:15][C:13]1([CH3:16])[CH2:12][O:11][C:10]([C:3]2[C:4]([CH3:9])=[CH:5][C:6]([C:18]([CH3:20])([CH3:19])[C:17]#[N:21])=[CH:7][C:2]=2[F:1])=[N:14]1

Participants

6

Reactant 4

HCID 6559IsobutyronitrileHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66742723HCID 66742723, compoundHCID 86587134Acetonitrile dry ice

Product 1

HCID 66742829HCID 66742829, compoundYield 99.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

A flask containing a solution of 2-(2,4-difluoro-6-methylphenyl)-4,4-dimethyl-4,5-dihydrooxazole (14.84 g, 65.9 mmol) and isobutyronitrile (9.11 g, 132 mmol) in dry tetrahydrofuran (130 ml) was cooled to −15 to −20° C. (acetonitrile/dry ice bath) under an argon atmosphere. A solution of potassium bis(trimethylsily) amide (171 ml, 0.5M in toluene) was added via slow drop-wise addition. The mixture was stirred for 30 minutes at −15° C. and then gradually warmed to 15° C. over about 1.5 hours. The material was quenched via the addition of a saturated solution of aqueous ammonium chloride (100 ml). Water (80 ml) and diethyl ether (50 ml) were added and the material was transferred to a reparatory funnel and the organic phase was collected. This was washed with an equal volume of water and the organic phase was collected. The aqueous phases were back extracted with ether (2×100 ml) and the combined organic phases were dried over magnesium sulfate, filtered and concentrated in vacuo. The material was purified by chromatography on silica gel eluting with 60% ethyl acetate/hexane to provide semi-pure product as a golden yellow oil (18 g, 75% pure). This material was used “as is” in subsequent steps. (M+H)+=275 m/e.

Workup

  1. temperaturegradually warmed to 15° C. over about 1.5 hours
  2. customThe material was quenched via the addition of a saturated solution of aqueous ammonium chloride (100 ml)
  3. additionWater (80 ml) and diethyl ether (50 ml) were added
  4. customthe material was transferred to a reparatory funnel
  5. customthe organic phase was collected
  6. washThis was washed with an equal volume of water
  7. customthe organic phase was collected
  8. extractionThe aqueous phases were back extracted with ether (2×100 ml)
  9. dry with materialthe combined organic phases were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe material was purified by chromatography on silica gel eluting with 60% ethyl acetate/hexane

Sources & evidence

ORD record
ord-cda248a25af5438d92002267ba0499b2
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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