M-Cresol → HCID 21962609, compound

HRID 2211935Notes

Reaction equation

HRID 2211935 reaction equation
[CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:8].[CH:9]([C:11]([CH3:13])=[O:12])=[CH2:10].C(N)C.N1C=CN=C1>C(Cl)(Cl)Cl>[CH3:8][C:2]1[CH:1]=[C:6]([CH:5]=[CH:4][CH:3]=1)[O:7][CH2:10][CH2:9][C:11](=[O:12])[CH3:13]

Participants

6

Reactant 4

HCID 342M-CresolHCID 795ImidazoleHCID 6341EthylamineHCID 6570Methyl vinyl ketone

Product 1

HCID 21962609HCID 21962609, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To m-Cresol (4.0 g, 37 mmol), methyl vinyl ketone (3.2 mL, 37 mmol) in chloroform (25 mL), was added diispropyl ethyl amine. The mixture was heated at reflux for 16 h, allowed to cool to room temperature and evaporated. The residue has 50% product and 50% starting material. The starting material was separated as t-butyldimethyl silyl ether. The product was isolated via plug filteration using silica gel 50% hexane/ethyl acetate. Yield 4.5 g (68%). As an alternative purification procedure, the crude reaction mixture was evaporated, dissolved in DMF (0.2M) and 0.5 equivalents of imidazole and 0.5 equivalents of tBDMSCI were added. The reaction was stirred for 3 hr at room temperature and then the solvents were removed in vacuo. To the residue was added 75 mL ethyl acetate and 75 mL water (ratio of 1/1). The ethyl acetate layer was separated and dried over Na2SO4. The solvents were removed in vacuo. The crude material was placed on a pad of silical gel and the silylated m-cresol was removed with hexanes. The product was obtained by eluting with 5-10% ethyl acetate in hexanes. The solvents were removed in vacuo to give the desired product. 1H(CDCl3):7.15 (t, 1H), 6.65-6.80(m, 2H), 4.25 (t, 2H), 2.75 (t, 2H), 2.25 and 2.35 (2 s, 3H each).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. customevaporated
  4. customThe starting material was separated as t-butyldimethyl silyl ether
  5. customThe product was isolated via plug filteration
  6. customAs an alternative purification procedure
  7. customthe crude reaction mixture
  8. customwas evaporated
  9. dissolutiondissolved in DMF (0.2M)
  10. customthe solvents were removed in vacuo
  11. additionTo the residue was added 75 mL ethyl acetate and 75 mL water (ratio of 1/1)
  12. customThe ethyl acetate layer was separated
  13. dry with materialdried over Na2SO4
  14. customThe solvents were removed in vacuo
  15. customthe silylated m-cresol was removed with hexanes
  16. customThe product was obtained
  17. washby eluting with 5-10% ethyl acetate in hexanes
  18. customThe solvents were removed in vacuo

Sources & evidence

ORD record
ord-c51825f579f04219a56f09ef5ea43f8c
Source dataset
uspto-grants-2006_09
Patent number
US07101878B1

Reaction notes

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