Sulfuric Acid → 3-(3,4-Dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonylbutyric acid ethyl ester

HRID 1977694Notes

Reaction equation

HRID 1977694 reaction equation
CS(CSC)=O.C([Li])C[CH2:9][CH3:10].[CH2:12]([O:14][C:15](=[O:33])[C:16](=[CH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=1)[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:13].[Cl-].[NH4+].[CH:36]([O-])([O-:40])[O:37][CH2:38][CH3:39].S(=O)(=O)(O)O.C(=O)([O-])O.[Na+]>O1CCCC1.C(O)C.CCCCCC>[CH2:20]([O:19][C:17](=[O:18])[CH:16]([C:15]([O:14][CH2:12][CH3:13])=[O:33])[CH:22]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH3:32])[CH:24]=1)[CH:36]([O:40][CH2:9][CH3:10])[O:37][CH2:38][CH3:39])[CH3:21]

Participants

11

Reactant 7

HCID 1118Sulfuric AcidHCID 25517Ammonium ChlorideHCID 99129Methyl (methylsulfinyl)methyl sulfideHCID 335552Diethyl 2-(3,4-dimethoxybenzylidene)malonateHCID 516892Sodium BicarbonateHCID 53630039EthylorthoformateHCID 178418339Butyllithium

Product 1

HCID 155213723-(3,4-Dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonylbutyric acid ethyl esterYield 79.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

24 ml of dried tetrahydrofuran solution of 2.34 g (18.81 mM) of methyl methylsulfinyl-methyl sulfide was cooled to 0° C. A hexane solution of n-butyl lithium (18.81 mM) was added dropwise to the solution and was stirred for around 30 minutes at the same temperature. The solution was cooled to −78° C., and solution of 5.00 g (15.47 mM) 3,4-dimethoxybenzylidenemalonic acid diethyl ester in 2 ml of dried tetrahydrofuran was added. The solution thus obtained was heated gradually to room temperature, poured to an aqueous ammonium chloride solution, and was extracted with diethyl ether. The organic extract was dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo to obtain 6.70 g crude product of brown oily 3-(3,4-dimethoxyphenyl)-2-ethoxycarbonyl-4-methylsulfinyl-4-methylthiobutyric ethyl ester. The crude product was dissolved in 25 ml of anhydrous ethanol, 3.09 g (20.88 mM) of ethyl orthoformate and 0.25 ml of sulfuric acid were added thereto, and the mixture was stirred for 3 days at room temperature. The solution was poured to an aqueous sodium hydrogencarbonate under ice cooling and was extracted with diethyl ether. The organic extract was dried, then the solvent was evaporated in vacuo to obtain a brown oily crude product. The crude product was purified by chromatography. The product was concentrated and dried in vacuo to obtain 5.08 g of yellow oily 3-(3,4-dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonylbutyric acid ethyl ester (yield 79.5%).

Workup

  1. customThe solution thus obtained
  2. temperaturewas heated gradually to room temperature
  3. extractionwas extracted with diethyl ether
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated in vacuo
  7. customto obtain 6.70 g crude product of brown oily 3-(3,4-dimethoxyphenyl)-2-ethoxycarbonyl-4-methylsulfinyl-4-methylthiobutyric ethyl ester
  8. stirringthe mixture was stirred for 3 days at room temperature
  9. extractionwas extracted with diethyl ether
  10. extractionThe organic extract
  11. customwas dried
  12. customthe solvent was evaporated in vacuo
  13. customto obtain a brown oily crude product
  14. customThe crude product was purified by chromatography
  15. concentrationThe product was concentrated
  16. customdried in vacuo

Sources & evidence

ORD record
ord-1b60709f39a9433d922aedcea364dd78
Source dataset
uspto-grants-2001_05
Patent number
US06235739B1

Reaction notes

Loading…