Bromide ion → E-7-(4-Methoxyphenyl)hept-4-enoic acid

HRID 431816Notes

Reaction equation

HRID 431816 reaction equation
[C:1]1([CH2:7][CH2:8]/[CH:9]=[CH:10]/[CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:16](=[O:25])CCC1C=CC=CC=1.[Li].C(O[PH+](CC(OCC)=O)OCC)C.[Br-].[Na].C(OCC)(=O)CC(OCC)=O>O1CCCC1>[CH3:16][O:25][C:4]1[CH:5]=[CH:6][C:1]([CH2:7][CH2:8]/[CH:9]=[CH:10]/[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:2][CH:3]=1

Participants

9

Reactant 7

HCID 259Bromide ionHCID 7707BenzenepropanalHCID 7761Diethyl MalonateHCID 3028194LithiumHCID 5360545SodiumHCID 9899164E-7-Phenylhept-4-enoic acidHCID 22731479Ethyl diethoxyphosphonioacetate

Product 1

HCID 9921036E-7-(4-Methoxyphenyl)hept-4-enoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

E-7-(4-Methoxyphenyl)hept-4-enoic acid was prepared in the same fashion as E-7-phenylhept-4-enoic acid by substituting 3-(4-methoxyphenyl) propional for dihydrocinnamaldehyde as the starting material in the synthetic sequence. 3-(4-methoxyphenyl)propional was combined with the lithium salt of ethyl diethoxyphosphonioacetate in tetrahydrofuran at room temperature. The resulting unsaturated ester, ethyl 5-(4-methoxyphenyl)pent-2-enoate, was purified by chromatography. The unsaturated ester was then reduced with excess diisobutylaluminum hydride in tetrahydrofuran at −78° C. The purified alcohol was then converted to the bromide, E-1-bromo-5-(4-methoxyphenyl)pent-2-ene, by reaction with triphenylphosphine and carbon tetrabromide in methylene chloride at 0°C. The purified bromide was then used to alkylate the sodium salt of diethyl malonate to provide the diester, methyl E-1-carbomethoxy-5-(4-methoxyphenyl)hept-4-enoate. The diester was purified by chromatography and then subjected to saponification using methanolic sodium hydroxide. The diacid was purified by acid/ibase extraction and then used directly in the next step of the reaction sequence. Heating the neat diacid at 170° C. (under Ar) for 30 minutes effected decarboxylation. The product, E-7-(4-methoxyphenyl)hept-4-enoic acid, was obtained in greater than 95% purity. Any residual diacid was removed by dissolving the acid in hexane and filtering. All compounds in the reaction sequence were fully characterized by spectral analysis and new compounds were analyzed by combustion analysis.

Workup

  1. customThe resulting unsaturated ester, ethyl 5-(4-methoxyphenyl)pent-2-enoate, was purified by chromatography
  2. customwas then reduced with excess diisobutylaluminum hydride in tetrahydrofuran at −78° C
  3. customThe purified alcohol was then converted to the bromide, E-1-bromo-5-(4-methoxyphenyl)pent-2-ene, by reaction with triphenylphosphine and carbon tetrabromide in methylene chloride at 0°C

Sources & evidence

ORD record
ord-18e6faaa3bf64bb2b803e6c609be906b
Source dataset
uspto-grants-2003_12
Patent number
US06660770B2

Reaction notes

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