1,3-dihydro-4-methyl-2H-imidazol-2-one → Ethyl 2,3-dihydro-5-methyl-epsilon-2-dioxo-1H-imidazole-4-hexanoate

HRID 2231380Notes

Reaction equation

HRID 2231380 reaction equation
[CH3:1][C:2]1[NH:3][C:4](=[O:7])[NH:5][CH:6]=1.[Al+3].[Cl-].[Cl-].[Cl-].C([CH:14]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:16][CH2:17][C:18](Cl)=[O:19])C.CO.C(OCC)(=O)C>S1(CCCC1)(=O)=O.C(Cl)(Cl)Cl.OP(O)=O.O[Mo](O)(=O)=O>[CH3:1][C:2]1[NH:3][C:4](=[O:7])[NH:5][C:6]=1[C:18](=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14][C:21]([O:23][CH2:24][CH3:25])=[O:22]

Participants

8

Reactant 4

HCID 709351,3-dihydro-4-methyl-2H-imidazol-2-oneHCID 6451240Aluminum(III) ChlorideHCID 21584119Ethylacetate methanolHCID 57153212HCID 57153212, compound

Product 1

HCID 2166009Ethyl 2,3-dihydro-5-methyl-epsilon-2-dioxo-1H-imidazole-4-hexanoateYield 109.2%

Reagents, catalysts & solvents 3

HCID 21863154Dihydroxy(dioxo)molybdenum;phosphonic acidCatalystHCID 6212ChloroformSolventHCID 31347SulfolaneSolvent

Conditions

Temperature
75 °C

Procedure

A slurry of this crude intermediate [containing 10.6 g (0.108 mol) of 4-methyl-4-imidazolin-2-one by assay] in 51.8 g of sulfolane and 100 ml of chloroform was cooled to ice bath temperature in a 3-necked round bottom flask equipped with reflux condenser, nitrogen inlet, nitrogen outlet, mechanical stirrer and addition funnel and 71.8 g (0.540 mol) of AlCl3 added portionwise. After the addition was complete, the temperature of the bath was raised to 75° C. and 29.0 g (0.151 mol) of ethyl 5-ethoxycarbonylpentanoyl chloride added dropwise over a 60 minute period. On heating an additional 1.5 hours, tlc (silica gel, methanol/ethyl acetate 1:4, UV followed by phosphomolybdic acid visualization) suggested the complete consumption of starting material and the formation of the desired ketoester. The reaction mixture was then poured onto 500 ml of ice containing 16 g of sodium carbonate dissolved in 50 ml of water. The aqueous hydrolysis mixture was stirred rapidly while 400 ml of ethyl ether was added. After 15 minutes the precipitated solid was removed by filtration, washed with ether and dried overnight under vacuum to afford 30.0 g of tan solid shown to be 76% pure by hplc analysis (83% yield corrected for purity). The solid was recrystallized from 1:1 ethanol:water to yield 16.7 g of purified title product, homogeneous by hplc and tlc, m.p. 170°-172° C., identical in physical properties to the product of the preceding Example.

Workup

  1. customequipped
  2. temperaturewith reflux
  3. additioncondenser, nitrogen inlet, nitrogen outlet, mechanical stirrer and addition funnel
  4. additionAfter the addition
  5. temperatureOn heating an additional 1.5 hours
  6. customthe complete consumption of starting material
  7. additionThe reaction mixture was then poured onto 500 ml of ice containing 16 g of sodium carbonate
  8. dissolutiondissolved in 50 ml of water
  9. additionwas added
  10. customAfter 15 minutes the precipitated solid was removed by filtration
  11. washwashed with ether
  12. customdried overnight under vacuum

Sources & evidence

ORD record
ord-c343bb40cf294f94b3f1e163579c5ed4
Source dataset
uspto-grants-1988_11
Patent number
US04782165

Reaction notes

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