Acetic Acid → HCID 67102427, compound

HRID 1988177Notes

Reaction equation

HRID 1988177 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[O:11][CH3:12])=O.[C:13]([CH2:15][C:16]([O:18][CH3:19])=[O:17])#[N:14].C(N)C1C=CC=CC=1.C(O)(=O)C>C1(C)C=CC=CC=1>[CH3:19][O:18][C:16](=[O:17])[C:15]([C:13]#[N:14])=[C:2]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[O:11][CH3:12])[CH3:1]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7504BenzylamineHCID 7747Methyl cyanoacetateHCID 1428871-(4-Fluoro-2-methoxyphenyl)ethan-1-one

Product 1

HCID 67102427HCID 67102427, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a round bottom flask fitted with a Dean-Stark trap was added a mixture of 19.54 g (116 mmol) of 4-fluoro-2-methoxyacetophenone, 15.29 mL (174 mmol) of methyl cyanoacetate, 1.42 mL (13 mmol) of benzylamine, and 6.6 mL of acetic acid in 170 mL of toluene and the mixture was warmed to reflux. The reaction was monitored by TLC (EtOAc-hexanes, 2:8). After 18 hours, the reaction was then cooled and concentrated in vacuo to afford a dark, orange oil. The crude oil was distilled at 130° C. under vacuum (Kugelrohr) to remove unreacted 4-fluoro-2-methoxyactophenone. The crude product was then passed through a pad of silica gel using a 10% EtOAc in a 1:1 mixture of dichloromethane in hexanes to afford 27.64 g (95%) of 2-cyano-3-(4-fluoro-2-methoxyphenyl)but-2-enoic acid methyl ester as a light orange oil which was a mixture of geometric isomers.

Workup

  1. customTo a round bottom flask fitted with a Dean-Stark trap
  2. additionwas added
  3. temperaturethe mixture was warmed to reflux
  4. temperaturethe reaction was then cooled
  5. concentrationconcentrated in vacuo
  6. customto afford a dark, orange oil
  7. distillationThe crude oil was distilled at 130° C. under vacuum (Kugelrohr)
  8. customto remove unreacted 4-fluoro-2-methoxyactophenone
  9. additionin a 1:1 mixture of dichloromethane in hexanes

Sources & evidence

ORD record
ord-fcbe893ab8564e86a17d7a2ac1679cd3
Source dataset
uspto-grants-2009_06
Patent number
US07553966B2

Reaction notes

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