Hydrochloric Acid → 4-Chloro-2-(2-methoxyphenyl)quinazoline

HRID 2062146Notes

Reaction equation

HRID 2062146 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[NH:18][C:17](=O)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1.P(Cl)(Cl)([Cl:22])=O.CN(C)C1C=CC=CC=1.Cl>>[Cl:22][C:17]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=[C:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[N:18]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 949N,N-Dimethylaniline2×HCID 24813Phosphorus oxychlorideHCID 1354360052-(2-methoxyphenyl)-3H-quinazolin-4-one

Product 1

HCID 180716414-Chloro-2-(2-methoxyphenyl)quinazoline

Procedure

A suspension of 2-(2-methoxyphenyl)quinazolin-4(3H)-one (567 g, 2.1 mol) in phosphoryl chloride (2 L, 21 mol) and a catalytic amount of N,N-dimethyl aniline was brought to reflux. The reaction started immediately with the evolution of gas (HCl) upon the addition of N,N-dimethyl aniline. After the production of gas had ceased the mixture was cooled to room temperature. The excess POCl3 was evaporated. The resulting dark solution was cooled to room temperature and slowly poured on ice and water, while maintaining the temperature below 5° C. The cold suspension was extracted with dichloromethane. The extract was dried over sodium sulfate and filtered, and the solvent was removed in vacuo. The crude material was purified by column chromatography (silica gel, CH2Cl2). Yield: 189 g (33%) of 4 chloro-2-(2-methoxyphenyl) quinazoline. 1H-NMR (300 MHz, Me2SO-d6): δ 3.85 (s, 3H), 7.15 (t, 1H), 7.25 (d, 1H), 7.60 (t, 2H), 7.70 (d, 1H), 7.8 (d, 1H), 7.9 (t, 1H), 8.2 (d, 1H).

Workup

  1. temperatureto reflux
  2. customThe excess POCl3 was evaporated
  3. temperatureThe resulting dark solution was cooled to room temperature
  4. additionslowly poured on ice and water
  5. temperaturewhile maintaining the temperature below 5° C
  6. extractionThe cold suspension was extracted with dichloromethane
  7. dry with materialThe extract was dried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customThe crude material was purified by column chromatography (silica gel, CH2Cl2)

Sources & evidence

ORD record
ord-de276b656a4e4abc81a2fae070290f1f
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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