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

HRID 424606Notes

Reaction equation

HRID 424606 reaction equation
CC(S[CH:7](S(C)=O)[CH3:8])S(C)=O.C([Li])CCC.[CH2:17]([O:19][C:20](=[O:38])[C:21](=[CH:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:18].[Cl-].[NH4+].[CH:41]([O-])([O-:45])[O:42][CH2:43][CH3:44].S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>O1CCCC1.CCCCCC.C(O)C>[CH2:25]([O:24][C:22](=[O:23])[CH:21]([C:20]([O:19][CH2:17][CH3:18])=[O:38])[CH:27]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=1)[CH:41]([O:45][CH2:7][CH3:8])[O:42][CH2:43][CH3:44])[CH3:26]

Participants

11

Reactant 7

HCID 1118Sulfuric AcidHCID 25517Ammonium ChlorideHCID 335552Diethyl 2-(3,4-dimethoxybenzylidene)malonateHCID 516892Sodium BicarbonateHCID 53630039EthylorthoformateHCID 54140058Methylmethylsulfinylmethyl sulfideHCID 178418339Butyllithium

Product 1

HCID 155213723-(3,4-Dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonylbutyric acid ethyl esterYield 112.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of methyl methylsulfinyl-methylsulfide (2.34 g, 18.81 M) in dry tetrahydrofuran (24 ml) was cooled to 0° C., and to this solution a solution of butyl lithium in hexane (18.81 mM) was added dropwise, which was stirred at the temperature as it was for 30 minutes. Then, the solution was cooled to −78° C., and a solution of 3,4-dimethoxybenzylidene malonic acid diethyl ester (5.00 g, 15.47 mM) in dry tetrahydrofuran (2 ml) was added. The solution obtained was gradually warmed to room temperature, was poured into an aqueous solution of ammonium chloride, extracted with diethylether, and after drying the organic extract over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure to obtain a crude product (6.70 g) of a brown oil of 3-(3,4-dimethoxyphenyl)-2-ethoxycarbonyl-4-methylsulfinyl-4-methylthio butyric acid ethyl ester. This was dissolved in dry ethanol (25 ml), and then ethyl orthoformate (3.09 g, 20.88 mM) and sulfuric acid (0.25 ml) were added and stirred at room temperature for 3 days. This solution was poured into an aqueous solution of sodium bicarbonate under cooling on ice, extracted with diethylether, and after the organic extract was dried, the solvent was evaporated under reduced pressure to obtain an oily crude product. The crude product was purified by flash chromatography (SiO2: eluted with ethyl acetate). It was concentrated under reduced pressure and dried to obtain a yellow oil of 3-(3,4-dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonyl butyric acid ethyl ester (5.08 g, yield 79.5%).

Workup

  1. customThe solution obtained
  2. temperaturewas gradually warmed to room temperature
  3. extractionextracted with diethylether
  4. customafter drying the
  5. extractionorganic extract over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customto obtain a crude product (6.70 g) of a brown oil of 3-(3,4-dimethoxyphenyl)-2-ethoxycarbonyl-4-methylsulfinyl-4-methylthio butyric acid ethyl ester
  8. stirringstirred at room temperature for 3 days
  9. temperatureunder cooling on ice
  10. extractionextracted with diethylether
  11. extractionafter the organic extract
  12. customwas dried
  13. customthe solvent was evaporated under reduced pressure
  14. customto obtain an oily crude product
  15. customThe crude product was purified by flash chromatography (SiO2: eluted with ethyl acetate)
  16. concentrationIt was concentrated under reduced pressure
  17. customdried

Sources & evidence

ORD record
ord-63b1ef925e534010af58f6ccd70dc7a2
Source dataset
uspto-grants-2012_01
Patent number
US08106053B2

Reaction notes

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