Sulfuric Acid → 4-(4-Chlorophenyl)-4-methyl-2-oxo-valeric acid

HRID 2055023Notes

Reaction equation

HRID 2055023 reaction equation
C([O:3][C:4](=[O:17])[CH:5](P(OCC)(OCC)=O)[O:6]CC)C.C([N-]C(C)C)(C)C.[Li+].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([CH3:37])([CH3:36])[CH:34]=O)=[CH:29][CH:28]=1.S(=O)(=O)(O)O>O1CCCC1.O1CCCC1.CCCCCCC.C1(C)C=CC=CC=1>[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([CH3:37])([CH3:36])[CH2:34][C:5](=[O:6])[C:4]([OH:3])=[O:17])=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 314825ethyl 2-diethoxyphosphoryl-2-ethoxyacetateHCID 2724682Lithium diisopropylamideHCID 114353342-(4-Chlorophenyl)-2-methylpropanal

Product 1

HCID 219488514-(4-Chlorophenyl)-4-methyl-2-oxo-valeric acidYield 81.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22168748HCID 22168748, compoundSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 15.04 g of 2-diethylphosphono-2-ethoxyacetic acid-ethyl ester in 50 ml of tetrahydrofuran is mixed while being cooled with ice within 20 minutes with 30 ml of a 2 M solution of lithium diisopropylamide in tetrahydrofuran-heptane-toluene, and it is stirred for 15 minutes at 0° C. Within 30 minutes, a solution of 10.2 g of 2-(4-chlorophenyl)-2-methylpropanal in 50 ml of tetrahydrofuran is added in drops thereto at 0° C. After 20 hours at room temperature, 2N sulfuric acid is added, it is extracted with ethyl acetate, dried (Na2SO4) and concentrated by evaporation. The crude product is saponified with 200 ml of 2 M sodium hydroxide solution/400 ml of ethanol. 13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid while being stirred vigorously, is obtained. After extraction with ethyl acetate and washing with water, 10.9 g of 4-(4-chlorophenyl)-4-methyl-2-oxo-valeric acid is obtained as a red oil.

Workup

  1. waitWithin 30 minutes
  2. customat 0° C
  3. waitAfter 20 hours at room temperature
  4. extractionit is extracted with ethyl acetate
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated by evaporation
  7. temperature13.8 g of acid, which is refluxed for 3 hours with 300 ml of 2N sulfuric acid and 100 ml of glacial acetic acid
  8. stirringwhile being stirred vigorously
  9. customis obtained
  10. extractionAfter extraction with ethyl acetate
  11. washwashing with water

Sources & evidence

ORD record
ord-ee5bce82cc2b434ca71bce7246bad4b2
Source dataset
uspto-grants-2008_02
Patent number
US07329753B2

Reaction notes

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