Benzaldehyde → HCID 53691566, compound

HRID 2189041Notes

Reaction equation

HRID 2189041 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([C:15]1[CH:20]=[CH:19][C:18]([CH:21]([O:24][Si](C)(C)C)C#N)=[CH:17][CH:16]=1)[CH3:14].[CH:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[Cl-].[NH4+]>COCCOC>[CH2:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:24])[CH:29]([OH:36])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:17][CH:16]=1)[CH3:14]

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 23540703HCID 23540703, compoundHCID 178418339Butyllithium

Product 1

HCID 53691566HCID 53691566, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
-60 °C

Procedure

Dissolve 290 ml (2.069 mol) diisopropylamine in 3.6 liters DME and precool to −78° C. Add 820 ml (2.05 mol) n-butyllithium (2.5 M solution in hexane) dropwise in the space of approx. 20 min (temperature<−60° C.). After 15 min at −60° C., add a solution of 435 g (1.864 mol) (4-ethylphenyl)[(trimethylsilyl)oxy]acetonitrile in 1.4 liters DME dropwise (temperature<−60° C.). Stir the mixture for a further 30 min at −60° C., before adding a solution of 189.5 ml (1.864 mol) benzaldehyde in 1.4 liters DME (time approx. 20 min, temperature −60° C.). Heat the mixture over a period of 4 h to RT, before adding 7 liter satd. ammonium chloride solution. Extract the reaction mixture with ethyl acetate. After phase separation, wash the organic phase with satd. ammonium chloride solution, dry, and concentrate by vacuum evaporation. Dissolve the residue in 7 liters dioxan and 5 liters methanol, and add 6 liters 1 N hydrochloric acid. Stir the mixture overnight at RT, then, after adding 11 liters satd. sodium chloride solution, extract with 6.5 liters ethyl acetate. Wash the organic phase with water and with satd. sodium chloride solution, dry, and concentrate by vacuum evaporation. Dissolve the residue in 2 liters diisopropyl ether, add seed crystals and stir for 2 h. The precipitated solid is filtered with suction, washed with 300 ml diisopropyl ether and petroleum ether and dried under vacuum. Concentrate the mother liquor, and after storing for 2 days at 4° C., again filter off the precipitated solid with suction, wash with approx. 100 ml diisopropyl ether and petroleum ether and dry under vacuum. On combining the two solids, 154.9 g (34% of theor.) of the target product is obtained.

Workup

  1. customprecool to −78° C
  2. temperatureHeat the mixture over a period of 4 h to RT
  3. additionbefore adding 7 liter
  4. extractionExtract the reaction mixture with ethyl acetate
  5. customAfter phase separation
  6. washwash the organic phase with satd
  7. dry with materialammonium chloride solution, dry
  8. concentrationconcentrate by vacuum evaporation
  9. dissolutionDissolve the residue in 7 liters dioxan
  10. addition5 liters methanol, and add 6 liters 1 N hydrochloric acid
  11. stirringStir the mixture overnight at RT
  12. additionafter adding 11 liters
  13. extractionsodium chloride solution, extract with 6.5 liters ethyl acetate
  14. washWash the organic phase with water
  15. dry with materialsodium chloride solution, dry
  16. concentrationconcentrate by vacuum evaporation
  17. dissolutionDissolve the residue in 2 liters diisopropyl ether
  18. additionadd seed crystals
  19. stirringstir for 2 h
  20. filtrationThe precipitated solid is filtered with suction
  21. washwashed with 300 ml diisopropyl ether and petroleum ether
  22. customdried under vacuum
  23. concentrationConcentrate the mother liquor
  24. waitafter storing for 2 days at 4° C.
  25. filtrationagain filter off the precipitated solid with suction
  26. washwash with approx. 100 ml diisopropyl ether and petroleum ether
  27. customdry under vacuum
  28. customis obtained

Sources & evidence

ORD record
ord-5ad07c1673694fb68349d20653398617
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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