1,1'-Carbonyldiimidazole → Ethyl 4-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-1,3-oxazin-3-yl)-4-methyl-3-oxo-pentanoate

HRID 1274875Notes

Reaction equation

HRID 1274875 reaction equation
C([Mg]Br)(C)C.[C:6]([O:12][CH2:13][CH3:14])(=[O:11])[CH2:7][C:8]([O-:10])=O.[CH3:15][C:16]1[O:21][CH2:20][N:19]([C:22](C)([CH3:26])[C:23](O)=O)[C:18](=[O:28])[C:17]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N-]1C=CN=C1>O1CCCC1.CCOCC>[CH3:15][C:16]1[O:21][CH2:20][N:19]([C:22]([CH3:26])([CH3:23])[C:8](=[O:10])[CH2:7][C:6]([O:12][CH2:13][CH3:14])=[O:11])[C:18](=[O:28])[C:17]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 3386966ImidazolateHCID 3595298Propanedioic acid, monoethyl esterHCID 221182822-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acidHCID 178418365HCID 178418365, compound

Product 1

HCID 22118254Ethyl 4-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-1,3-oxazin-3-yl)-4-methyl-3-oxo-pentanoateYield 55.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

Isopropyl magnesium bromide (0.7M solution in tetrahydrofuran) was added to a solution of mono-ethyl malonate(1.44 g) in tetrahydrofuran at 0° C. The mixture was stirred at 20° C. for 0.5 hour and at 40° C. for 0.5 hour. 2-(2,3-Dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropionic acid (2 g) and carbonyldiimidazole(1.42 g) was stirred in tetrahydrofuran for 8 hours and the resulting imidazolide solution then added to the above mixture at 0° C., stirred at 20° C. for 3 hours and refluxed for 2 hours. The mixture was diluted (ether), washed (5% hydrochloric acid), dried (MgSO4),evaporated and the residue purified by column chromatography (ethyl acetate/hexane 1:2) to give ethyl 4-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-4-methyl-3-oxo-pentanoate (1.4 g), NMR 1.25(3H, t), 1.47(6H, s), 1.94(3H, s), 3.60(2H, s), 4.15(2H, q), 5.26(2H, s), 7.2-7.4(5H, m).

Workup

  1. stirringstirred at 20° C. for 3 hours
  2. temperaturerefluxed for 2 hours
  3. washwashed (5% hydrochloric acid), dried (MgSO4),evaporated
  4. customthe residue purified by column chromatography (ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-e4700d9ace5c4ff1a649617ba8520871
Source dataset
uspto-grants-2000_12
Patent number
US06159902

Reaction notes

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