Diethyl Malonate → HCID 13769247, compound

HRID 2232513Notes

Reaction equation

HRID 2232513 reaction equation
[H-].[Na+].[C:3]([O:11]CC)(=[O:10])[CH2:4][C:5](OCC)=O.[H][H].BrC[C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:19]=1>O1CCCC1.C(O)(=O)C>[C:28]1([C:20]2[N:19]=[C:18]([CH2:5][CH2:4][C:3]([OH:11])=[O:10])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 13769246HCID 13769246, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 13769247HCID 13769247, compoundYield 40.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

Sodium hydride (5.4 g, 80% strength in oil) is placed under nitrogen with anhydrous tetrahydrofuran (250 cc) and then, with the mixture cooled to about 5° C., diethyl malonate (25.6 g) is added. When the evolution of hydrogen has ceased, a solution of 4-bromomethyl-2-phenylquinazoline (23.9 g) in anhydrous tetrahydrofuran (100 cc) is added. After 1 hour's stirring at room temperature (approximately 20° C.), acetic acid (25 cc) is added, the solvent evaporated under reduced pressure and the residue taken up in concentrated hydrochloric acid (150 cc) and acetic acid (150 cc). The mixture is brought to 120° C. for 15 hours and evaporated again, water (200 cc) and ethyl ether (150 cc) are added and the mixture is alkalinised to pH 11 with sodium hydroxide solution. The organic phase is decanted and the aqueous solution washed with ethyl ether (2×100 cc). The aqueous phase is adjusted to pH 4 and extracted with ethyl acetate (2×100 cc). The organic phase is dried over magnesium sulphate and evaporated to dryness under reduced pressure. The residue is crystallized in ethyl acetate. 2-Phenyl-4-quinazolinepropanoic acid (9 g), m.p. 159° C., is obtained.

Workup

  1. additionis added
  2. customthe solvent evaporated under reduced pressure
  3. customevaporated again
  4. additionwater (200 cc) and ethyl ether (150 cc) are added
  5. customThe organic phase is decanted
  6. washthe aqueous solution washed with ethyl ether (2×100 cc)
  7. extractionextracted with ethyl acetate (2×100 cc)
  8. dry with materialThe organic phase is dried over magnesium sulphate
  9. customevaporated to dryness under reduced pressure
  10. customThe residue is crystallized in ethyl acetate

Sources & evidence

ORD record
ord-2011408fff314e279e5c90903ac52357
Source dataset
uspto-grants-1988_11
Patent number
US04788199

Reaction notes

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