Hydrochloric Acid → 4-Fluoro-4-methyl-3-oxopentanenitrile

HRID 929976Notes

Reaction equation

HRID 929976 reaction equation
[H-].[Na+].[F:3][C:4]([CH3:10])([CH3:9])[C:5](OC)=[O:6].[C:11](#[N:13])[CH3:12].Cl>C1COCC1.O>[F:3][C:4]([CH3:10])([CH3:9])[C:5](=[O:6])[CH2:12][C:11]#[N:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 9793744Methyl 2-Fluoro-2-methylpropionate

Product 1

HCID 866535074-Fluoro-4-methyl-3-oxopentanenitrileYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred suspension of 60% NaH/mineral oil (12.48 g, 0.31 mol) in dry THF at 75° C. was added dropwise methyl 2-fluoro-2-methylpropanoate (24 g, 0.2 mol) in dry acetonitrile (16 mL, 0.31 mol) over the course of 45 min. The resulting pale yellow suspension was heated at 70° C. overnight, whereupon analysis by TLC indicated a single new product. After cooling to rt, the mixture was poured into water, acidified to pH˜2 with 2N HCl, and extracted with diethyl ether (1 L). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-30% EtOAc in petroleum ether to afford 4-fluoro-4-methyl-3-oxopentanenitrile as a colorless oil (18 g, 72% yield). LC-MS (ESI) m/z 128 (M−H)+.

Workup

  1. temperatureAfter cooling to rt
  2. extractionextracted with diethyl ether (1 L)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with 0-30% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-a89e905e24e74df6a1a83b6240b9ad57
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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