Bromoacetonitrile → Ethyl 3-cyano-2,2-bis(4-fluorophenyl)propanoate

HRID 2408834Notes

Reaction equation

HRID 2408834 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:32][C:33]#[N:34]>O1CCCC1>[C:33]([CH2:32][C:8]([C:14]1[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=1)([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])#[N:34]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 54751768Ethyl 2,2-bis(4-fluorophenyl)acetate

Product 1

HCID 67357361Ethyl 3-cyano-2,2-bis(4-fluorophenyl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl 2,2-bis(4-fluorophenyl)acetate (0.28 g, 1.00 mmol) in dry tetrahydrofuran at −78° C. was added lithium bis(trimethylsilyl)amide (1.0 M in hexane) (1.00 mL, 1.00 mmol) dropwise via syringe under nitrogen. The reaction was brought to 0° C. and stirred for one hour. The reaction was re-cooled to −78° C. and then bromoacetonitrile (0.69 mL, 1.00 mmol) was added as a solution in tetrahydrofuran (30 mL). The reaction was stirred for 2 hours while the temperature was allowed to reach room temperature. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether. The combined organic extracts were washed with brine, dried with MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (10% ethyl acetate/hexanes) to obtain the title compound. MS (DCI+) m/z 333 (M+NH4)+.

Workup

  1. customwas brought to 0° C.
  2. stirringThe reaction was stirred for 2 hours while the temperature
  3. customto reach room temperature
  4. customThe reaction was quenched with saturated aqueous ammonium chloride solution
  5. extractionextracted with diethyl ether
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5dcde7ae18ae403b808f5f475812520d
Source dataset
uspto-grants-2014_08
Patent number
US08815869B2

Reaction notes

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