Benzeneacetonitrile, 3-fluoro- → Methyl 4-cyano-3-(p-fluorophenyl)-4-(m-fluorophenyl)butyrate

HRID 1198847Notes

Reaction equation

HRID 1198847 reaction equation
C[O-].[Na+].[F:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]#[N:13])[CH:8]=[CH:9][CH:10]=1.[F:14][C:15]1[CH:26]=[CH:25][C:18]([CH:19]=[CH:20][C:21]([O:23][CH3:24])=[O:22])=[CH:17][CH:16]=1>C1(C)C=CC=CC=1>[C:12]([CH:11]([C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([F:4])[CH:6]=1)[CH:19]([C:18]1[CH:17]=[CH:16][C:15]([F:14])=[CH:26][CH:25]=1)[CH2:20][C:21]([O:23][CH3:24])=[O:22])#[N:13]

Participants

5

Reactant 3

HCID 68145Benzeneacetonitrile, 3-fluoro-HCID 9587502-Propenoic acid, 3-(4-fluorophenyl)-, methyl esterHCID 10942334Sodium Methoxide

Product 1

HCID 14838737Methyl 4-cyano-3-(p-fluorophenyl)-4-(m-fluorophenyl)butyrateYield 95%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Sodium methoxide (3.0 g, 0.056 mol) is added in one portion to a stirred solution of m-fluorophenylacetonitrile (78.0 g, 0.577 mol) and methyl p-fluorocinnamate (100.0 g, 0.555 mol) in 700 mL of azeotropically dried toluene cooled in an ice bath under a nitrogen atmosphere. The reaction mixture is warmed to room temperature (18° C. to 24° C.) and stirred for five days. The mixture is concentrated under vacuum to yield a brown syrup which is partitioned between diethyl ether and water. The orange ether layer is washed three times with water, once with 1% aqueous hydrochloric acid, again with water and finally with a saturated aqueous sodium chloride solution. After stirring with magnesium sulfate, the filtrate is concentrated on a rotary evaporator using a water aspirator, followed by a vacuum pump at 0.5 mm Hg for eight hours. The title product is obtained in 95% yield (166.7 g) as a pinkish-orange semi-solid identified as an isomeric mixture of esters based on the proton and carbon magnetic resonance, infrared and chemical ionization mass spectra. The ratio of erythro/threo isomers is 62/38, respectively, based on the integrated areas of the CHCN doublets centered at δ4.38 (J=6 Hz) and 4.11 (J=7 Hz) ppm, respectively, in the proton nmr spectrum (CDCl3). Thin layer chromatography on Merck Silica Gel 60 F-254 plates (CH2Cl2) shows two major spots which are not completely resolved. Gas-liquid chromatography (10% SP 2100 programmed at 125°/five minutes to 250°/30 minutes at a rate of 10°/minute) indicates a 93 relative area percent purity for the isomeric esters.

Workup

  1. temperaturecooled in an ice bath under a nitrogen atmosphere
  2. concentrationThe mixture is concentrated under vacuum
  3. customto yield a brown syrup which
  4. customis partitioned between diethyl ether and water
  5. washThe orange ether layer is washed three times with water
  6. stirringAfter stirring with magnesium sulfate
  7. concentrationthe filtrate is concentrated on a rotary evaporator
  8. waitfollowed by a vacuum pump at 0.5 mm Hg for eight hours

Sources & evidence

ORD record
ord-c2d4daf8b064440cb4f781d1c75c1787
Source dataset
uspto-grants-1990_02
Patent number
US04898609

Reaction notes

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