Benzaldehyde → 4-METHOXYBENZOIN

HRID 1926862Notes

Reaction equation

HRID 1926862 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([O:24][Si](C)(C)C)C#N)=[CH:17][CH:16]=1.[CH:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[Cl-].[NH4+]>COCCOC>[OH:36][CH:29]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:21]([C:18]1[CH:19]=[CH:20][C:15]([O:14][CH3:13])=[CH:16][CH:17]=1)=[O:24]

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 10776145HCID 10776145, compoundHCID 178418339Butyllithium

Product 1

HCID 37914-METHOXYBENZOIN

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

According to the procedure in the literature [J. Chem. Soc. Perkin Trans. I, 1992, 2409-2417], dissolve 292 ml (2.08 mol) diisopropylamine in 3.6 litre 1,2-dimethoxyethane and cool to −78° C. Add 826 ml n-butyllithium solution (2.5 M in n-hexane, 2.066 mol) at a temperature below −60° C. Stir the mixture for a further 15 min at <−60° C. and then add a solution of 442 g (1.877 mol) (4-methoxyphenyl)[(trimethylsilyl)oxy]acetonitrile in 1.41 litre 1,2-dimethoxyethane dropwise at <−60° C. After further stirring for 30 min at −60° C., add a solution of 199.3 g (1.878 mol) benzaldehyde in 1.4 litre 1,2-dimethoxyethane in the space of 20 min at −60° C. Next, heat the reaction mixture slowly to RT in 4 h. Add 7 litre saturated ammonium chloride solution and extract with ethyl acetate. Wash the organic phase with saturated ammonium chloride solution, dry, and concentrate under vacuum. Take up the residue in 7 litre dioxan and 5 litre methanol, and add 6 litre 1 N hydrochloric acid. Stir the mixture for 3 h at RT, then add 3 litre saturated sodium chloride solution and extract the mixture with 6.5 litre ethyl acetate. Wash the organic phase with 1.0 litre 1 N sodium hydroxide solution and with saturated sodium chloride solution, dry, and concentrate under vacuum. Take up the residue in 2 litre diisopropyl ether, decant from the insoluble matter and seed with crystals. Stir the resultant suspension for 2 h at RT and then filter off the crystals with suction. Wash with 300 ml diisopropyl ether and petroleum ether and dry under vacuum. 236.8 g (47.8% of theor.) of the target compound is obtained.

Workup

  1. stirringAfter further stirring for 30 min at −60° C.
  2. temperatureNext, heat the reaction mixture slowly to RT in 4 h
  3. extractionextract with ethyl acetate
  4. washWash the organic phase with saturated ammonium chloride solution
  5. customdry
  6. concentrationconcentrate under vacuum
  7. addition5 litre methanol, and add 6 litre 1 N hydrochloric acid
  8. stirringStir the mixture for 3 h at RT
  9. additionadd 3 litre saturated sodium chloride solution
  10. extractionextract the mixture with 6.5 litre ethyl acetate
  11. washWash the organic phase with 1.0 litre 1 N sodium hydroxide solution
  12. dry with materialwith saturated sodium chloride solution, dry
  13. concentrationconcentrate under vacuum
  14. customdecant from the insoluble matter and seed with crystals
  15. stirringStir the resultant suspension for 2 h at RT
  16. filtrationfilter off the crystals with suction
  17. washWash with 300 ml diisopropyl ether and petroleum ether
  18. customdry under vacuum
  19. custom236.8 g (47.8% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-efd03f6c65394ad08e4dba7da981934a
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

Loading…