Hydrochloric Acid → HCID 18551169, compound

HRID 1266418Notes

Reaction equation

HRID 1266418 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([Mg]Br)[CH:6]=[CH:7][CH:8]=1.C[O:12][C:13](=[O:20])[C:14](=[O:19])[CH:15]=[C:16]([CH3:18])[CH3:17].C[Si](C)(C)Cl.Cl>O1CCCC1.C(OCC)(=O)C.CN1CCCN(C)C1=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:16]([CH3:18])([CH3:17])[CH2:15][C:14](=[O:19])[C:13]([OH:20])=[O:12])[CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 17935624HCID 17935624, compoundHCID 178490745HCID 178490745, compound

Product 1

HCID 18551169HCID 18551169, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-40 °C

Procedure

4.2 ml of a 0.6 m solution of 3-methoxyphenylmagnesium bromide in tetrahydrofuran is mixed at −70° C. with 257 mg of copper bromide-dimethylsulfide complex and then stirred at −40° C. for 20 minutes. It is cooled again to −70° C., and 0.33 ml of 1,3-dimethyl-tetrahydro-2-1H-pyrimidinone and a mixture of 400 mg of 4-methyl-2-oxo-3-pentenoic acid methyl ester (Liebigs Annalen [Liebigs Annals] 1974, 477) and 0.71 ml of trimethylchlorosilane in 3.5 ml of tetrahydrofuran are slowly added. It is stirred for one hour at −70° C. and then heated to room temperature. Then, 2N hydrochloric acid and ethyl acetate are added, the ethyl acetate phase is separated, it is concentrated by evaporation, and the residue is dissolved in 5 ml of dichloromethane. After 200 mg of tetrabutylammonium fluoride is added, it is left at room temperature for one hour, then washed with water, and the dichloromethane phase is dried (Na2SO4) and concentrated by evaporation. After chroma-tography on silica gel with hexane/ethyl acetate (97:3), 63 mg of 4-(3-methoxyphenyl)-4-methyl-2-oxo-valeric acid-methyl ester, which is mixed with 1 ml of potassium hydroxide in methanol (10%), is obtained. After 45 minutes, it is concentrated by evaporation, the residue is dissolved in water and extracted with diethyl ether. The aqueous phase is then acidified with 6N hydrochloric acid and extracted with diethyl ether. The diethyl ether phase is dried (Na2SO4) and concen-trated by evaporation. 50 mg of 4-(3-methoxyphenyl)-4-methyl-2-oxo-valeric acid is obtained.

Workup

  1. temperatureIt is cooled again to −70° C.
  2. additionare slowly added
  3. stirringIt is stirred for one hour at −70° C.
  4. temperatureheated to room temperature
  5. customthe ethyl acetate phase is separated
  6. concentrationit is concentrated by evaporation
  7. dissolutionthe residue is dissolved in 5 ml of dichloromethane
  8. additionAfter 200 mg of tetrabutylammonium fluoride is added
  9. waitit is left at room temperature for one hour
  10. washwashed with water
  11. dry with materialthe dichloromethane phase is dried (Na2SO4)
  12. concentrationconcentrated by evaporation
  13. additionAfter chroma-tography on silica gel with hexane/ethyl acetate (97:3), 63 mg of 4-(3-methoxyphenyl)-4-methyl-2-oxo-valeric acid-methyl ester, which is mixed with 1 ml of potassium hydroxide in methanol (10%)
  14. customis obtained
  15. waitAfter 45 minutes
  16. concentrationit is concentrated by evaporation
  17. dissolutionthe residue is dissolved in water
  18. extractionextracted with diethyl ether
  19. extractionextracted with diethyl ether
  20. dry with materialThe diethyl ether phase is dried (Na2SO4)
  21. customconcen-trated by evaporation

Sources & evidence

ORD record
ord-c08d306d40074aba9d4c92259e48eb36
Source dataset
uspto-grants-2003_04
Patent number
US06548534B2

Reaction notes

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