3-Hydroxybutyric Acid → Methyl 2-(4-Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-5-(4-methyl-6-oxo-1,3-dioxan-2-yl)nicotinate

HRID 483623Notes

Reaction equation

HRID 483623 reaction equation
[CH:1]([C:3]1[CH:4]=[N:5][C:6]([C:13]2[NH:14][C:15](=[O:22])[C:16]([CH:19]([CH3:21])[CH3:20])([CH3:18])[N:17]=2)=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])=[O:2].[OH:23][CH:24]([CH3:29])[CH2:25][C:26](O)=[O:27].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH:19]([C:16]1([CH3:18])[C:15](=[O:22])[NH:14][C:13]([C:6]2[N:5]=[CH:4][C:3]([CH:1]3[O:23][CH:24]([CH3:29])[CH2:25][C:26](=[O:27])[O:2]3)=[CH:12][C:7]=2[C:8]([O:10][CH3:11])=[O:9])=[N:17]1)([CH3:20])[CH3:21]

Participants

5

Reactant 3

HCID 4413-Hydroxybutyric AcidHCID 6101p-Toluenesulfonic acidHCID 15676632Methyl 5-formyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinate

Product 1

HCID 15676670Methyl 2-(4-Isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-5-(4-methyl-6-oxo-1,3-dioxan-2-yl)nicotinateYield 20%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of methyl 5-formyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinate (0.55 g, 0.0018 mol), 3-hydroxybutyric acid (0.28 g, 0.0027 mol) and a catalytic amount of para-toluenesulfonic acid in chloroform (25 mL) is heated at reflux temperature for 113 hours. During this time, water is removed by placement of an addition funnel containing 3 angstrom molecular sieves between the reaction flask and the reflux condensor. The reaction mixture is poured into aqueous saturated sodium bicarbonate and the layers are separated. The aqueous portion is extracted with additional methylene chloride and the combined organic extracts are dried over anhydrous magnesium sulfate and concentrated in vacuo to give a residue. The residue is purified by chromatography using silica gel and ethyl acetate in hexanes as eluant to yield the title compound (0.14 g, 20%) as a white solid, mp 65°-75° C., identified by IR and NMR spectral analyses.

Workup

  1. temperatureat reflux temperature for 113 hours
  2. customDuring this time, water is removed by placement of an addition funnel
  3. additioncontaining 3 angstrom molecular sieves between the reaction flask
  4. additionThe reaction mixture is poured into aqueous saturated sodium bicarbonate
  5. customthe layers are separated
  6. extractionThe aqueous portion is extracted with additional methylene chloride
  7. dry with materialthe combined organic extracts are dried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a residue
  10. customThe residue is purified by chromatography

Sources & evidence

ORD record
ord-ee45292c435b4cb9938bb9b8574ec21e
Source dataset
uspto-grants-1993_07
Patent number
US05225564

Reaction notes

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