Water → 2-Chloro-6-(2,4-difluoro-phenoxy)-quinazoline

HRID 1292862

Reaction equation

HRID 1292862 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](N)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[CH:8]=2)[N:3]=1.N(OC(C)(C)C)=O.O>C1COCC1>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 10906Tert-Butyl nitriteHCID 589051302-Chloro-6-(2,4-difluoro-phenoxy)-quinazolin-4-ylamine

Product 1

HCID 589051372-Chloro-6-(2,4-difluoro-phenoxy)-quinazolineYield 44.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Compound (1G) (21 g, 0.07 mol) was dissolved in THF (200 mL) and the solution added dropwise to a solution of t-butyl nitrite (16.5 mL, 0.14 mol) in THF (100 mL). The mixture was heated to reflux for 4 h, and after cooling to room temperature, the reaction mixture was poured into water and extracted with EtOAc (2×100 mL). The combined organic layers were dried over sodium sulfate and evaporated in vacuo. The crude product was purified by chromatography (silica gel, hexane: EtOAc, 4:1) giving 9.05 g of 2-chloro-6-(2,4-difluoro-phenoxy)-quinazoline (1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 h
  3. extractionextracted with EtOAc (2×100 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe crude product was purified by chromatography (silica gel, hexane: EtOAc, 4:1)

Sources & evidence

ORD record
ord-45a0ea38ba1044248779521f5f92f884
Source dataset
uspto-grants-2007_07
Patent number
US07238698B2

Linked notes

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