Diisopropylamine → 5-(2-Chlorophenyl)-2-methylenevaleric acid ethyl ester

HRID 2285749Notes

Reaction equation

HRID 2285749 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH2:13]([O:15][C:16](=[O:31])[CH:17]([C:28](=O)C)[CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[CH3:14]>O1CCCC1>[CH2:13]([O:15][C:16](=[O:31])[C:17](=[CH2:28])[CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[CH3:14]

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 56632933HCID 56632933, compoundHCID 178418339Butyllithium

Product 1

HCID 129320915-(2-Chlorophenyl)-2-methylenevaleric acid ethyl esterYield 40.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 104 ml of 15% strength butyl-lithium (in hexane), 19 g of diisopropylamine and 400 ml of tetrahydrofuran is stirred together at -78°; 39 g of 5-(2-chlorophenyl)-2-acetylvaleric acid ethyl ester [prepared from 3-(2-chlorophenyl)propyltosylate and ethyl acetoacetate] are added dropwise to the resulting admixture. The mixture thus obtained is stirred for a further 20 minutes. After removing the cooling bath, 19.4 g of paraformaldehyde (anhydrous) are added in portions to the mixture. After stirring the mixture for 1 hour, it is heated under reflux for 5 hours and left to stand overnight. The solid constituents are filtered off, and the filtrate is concentrated in a rotary evaporator. 500 ml of saturated sodium bicarbonate solution are added to the residue, and the mixture is stirred for 30 minutes. Extraction with methylene chloride and evaporation of the solvent yield (after purification by distillation) 14 g of 5-(2-chlorophenyl)-2-methylenevaleric acid ethyl ester of b.p. 95° to 98° C. under 0.005 mm Hg. The title compound is obtained analogously to Example 4a by oxidation.

Workup

  1. customThe mixture thus obtained
  2. stirringis stirred for a further 20 minutes
  3. customAfter removing the cooling bath, 19.4 g of paraformaldehyde (anhydrous)
  4. additionare added in portions to the mixture
  5. stirringAfter stirring the mixture for 1 hour
  6. temperatureit is heated
  7. temperatureunder reflux for 5 hours
  8. waitleft
  9. filtrationThe solid constituents are filtered off
  10. concentrationthe filtrate is concentrated in a rotary evaporator
  11. addition500 ml of saturated sodium bicarbonate solution are added to the residue
  12. stirringthe mixture is stirred for 30 minutes
  13. extractionExtraction
  14. customwith methylene chloride and evaporation of the solvent

Sources & evidence

ORD record
ord-493193cfef804593b296e1903a747af1
Source dataset
uspto-grants-1982_04
Patent number
US04324796

Reaction notes

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