Hydrochloric Acid → Dimethyl 4-cyano-4-(2-fluorophenyl)heptanedioate

HRID 617740Notes

Reaction equation

HRID 617740 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]#[N:10].[C:11]([O:15][CH2:16]C)(=[O:14])[CH:12]=[CH2:13].[OH-:18].[CH2:19]([N+](C)(C)C)[C:20]1[CH:25]=CC=CC=1.Cl.[C:31]([OH:35])(C)(C)C>CO>[C:9]([C:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])([CH2:13][CH2:12][C:11]([O:15][CH3:16])=[O:14])[CH2:19][CH2:20][C:25]([O:35][CH3:31])=[O:18])#[N:10]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 8821Ethyl AcrylateHCID 66854Benzyltrimethylammonium hydroxideHCID 67592Benzeneacetonitrile, 2-fluoro-

Product 1

HCID 21834548Dimethyl 4-cyano-4-(2-fluorophenyl)heptanedioate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-Fluorophenylacetonitrile (39.85 g, 0.29 mol) and ethyl acrylate (96 ml, 0.89 mol) were stirred at reflux in t-butanol (400 ml) as benzyltrimethylammonium hydroxide (40% solution in MeOH, 140 ml, 0.30 mol) was added portionwise over 48 h. The mixture was then evaporated to dryness, dissolved in ethyl acetate (1000 ml), washed with dilute HCl and brine, dried (Na2SO4) and evaporated to give an oil. This was dissolved in MeOH (300 ml), and a solution of methanolic HCl (formed by cautious addition of thionyl chloride (20 ml) to MeOH (200 ml)) was added. The solution was stirred at reflux for 2 h, evaporated, dissolved in ether, filtered, and evaporated again to yield the title compound (97.6 g, quantitative) as an amber oil.

Workup

  1. additionwas added portionwise over 48 h
  2. customThe mixture was then evaporated to dryness
  3. dissolutiondissolved in ethyl acetate (1000 ml)
  4. washwashed with dilute HCl and brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customto give an oil
  8. temperatureat reflux for 2 h
  9. customevaporated
  10. dissolutiondissolved in ether
  11. filtrationfiltered
  12. customevaporated again

Sources & evidence

ORD record
ord-eeafa3f819da4230a2fa9399f5939ba7
Source dataset
uspto-grants-1999_09
Patent number
US05952325

Reaction notes

Loading…