Tin tetrachloride → Ethyl 2-(p-tolyl)quinazoline-4-carboxylate

HRID 717328Notes

Reaction equation

HRID 717328 reaction equation
[CH3:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=O)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH2:23]([O:25][C:26](=[O:29])[C:27]#[N:28])[CH3:24].Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]2[N:28]=[C:27]([C:26]([O:25][CH2:23][CH3:24])=[O:29])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24287Tin tetrachlorideHCID 24819Phosphorus pentachlorideHCID 69336Ethyl cyanoformateHCID 7305694-Methyl-N-phenylbenzamide

Product 1

HCID 90410917Ethyl 2-(p-tolyl)quinazoline-4-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-methyl-N-phenylbenzamide (6 g, 28.40 mmol, 1.00 equiv) in toluene (60 mL) and PCl5 (7.13 g, 34.24 mmol, 1.20 equiv). The mixture was stirred for 2 h at 65° C. The mixture was concentrated under vacuum. The residue was diluted with 30 mL of PhCl. To the mixture was added 2-ethoxy-2-oxoacetonitrile (3.37 g, 34.01 mmol, 1.20 equiv), SnCl4 (12.5 g, 1.70 equiv). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 125° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was extracted with 3×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 4×100 mL of water. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:30). This resulted in 2.64 g (32%) of ethyl 2-(4-methylphenyl)quinazoline-4-carboxylate as a light green solid. MS (ESI) m/z 293 ([M+H]+).

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe mixture was concentrated under vacuum
  4. additionThe residue was diluted with 30 mL of PhCl
  5. customto react
  6. stirringwith stirring, overnight while the temperature
  7. temperaturewas maintained at 125° C. in an oil bath
  8. concentrationThe resulting mixture was concentrated under vacuum
  9. extractionThe residue was extracted with 3×100 mL of ethyl acetate
  10. washThe resulting mixture was washed with 4×100 mL of water
  11. dry with materialThe mixture was dried over anhydrous sodium sulfate
  12. concentrationconcentrated under vacuum
  13. customThis resulted in 2.64 g (32%) of ethyl 2-(4-methylphenyl)quinazoline-4-carboxylate as a light green solid

Sources & evidence

ORD record
ord-1dcef2e0fc7e46c988109bec74e090af
Source dataset
uspto-grants-2015_11
Patent number
US09193707B2

Reaction notes

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