Phosphorus oxychloride → 2-Chloro-6-(3,5-dimethoxyphenyl)-7-fluoroquinazoline

HRID 56467Notes

Reaction equation

HRID 56467 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][C:20]=2[F:21])[N:17]=[C:16](O)[N:15]=[CH:14]3)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(=O)(O)[O-].[Na+].O=P(Cl)(Cl)[Cl:30]>>[Cl:30][C:16]1[N:15]=[CH:14][C:13]2[C:18](=[CH:19][C:20]([F:21])=[C:11]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=3)[CH:12]=2)[N:17]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178493435HCID 178493435, compound

Product 1

HCID 1180366872-Chloro-6-(3,5-dimethoxyphenyl)-7-fluoroquinazolineYield 52%

Procedure

A solution of 6-(3,5-dimethoxyphenyl)-7-fluoroquinazolin-2-ol (2.0 g, 6.7 mmol) in POCl3 (30 mL) was heated at 135° C. for 2 hours. After that, the reaction solution was cooled to room temperature and dropwise added to saturated sodium bicarbonate solution (800 mL) at 0° C. The mixture was extracted with ethyl acetate (200 mL*3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (1.1 g, 52%) as a pale yellow solid. MS (ES+) C16H12ClFN2O2 requires: 318, found: 319 [M+H]+.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (200 mL*3)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8c2e25b713d14935b66cfa5e10c09cb3
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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