Triethylamine → 4-Chloro-6-(trifluoromethyl)quinazoline

HRID 1391899Notes

Reaction equation

HRID 1391899 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2O.P(Cl)(Cl)([Cl:18])=O.C(N(CC)CC)C>C(Cl)Cl>[Cl:18][C:6]1[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:2]([F:15])([F:14])[F:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178517998HCID 178517998, compound

Product 1

HCID 210750954-Chloro-6-(trifluoromethyl)quinazolineYield 54.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

6-Trifluoromethyl-quinazolin-4-ol (0.95 g, 4.44 mmol, 1 eq.), phosphorous oxychloride (2.48 mL, 26.6 mmol, 6 eq.) and triethylamine (3.71 mL, 26.6 mmol, 6 eq.) were refluxed for 2.5 hours. Stripped 3× from methylene chloride then dissolved in methylene chloride and rinsed 3× with saturated NaHCO3, 1× with brine. Dried and stripped in vacuo to give and amber oil. Purified over silica gel in 9:1 Hexanes/EtOAc. Obtained 560 mg of off-white solids as product. The product was used immediately in Ex 111 part C.

Workup

  1. washrinsed 3× with saturated NaHCO3, 1× with brine
  2. customDried
  3. customto give
  4. customPurified over silica gel in 9:1 Hexanes/EtOAc

Sources & evidence

ORD record
ord-61a6921f952342c88d4555410d3b35aa
Source dataset
uspto-grants-2008_03
Patent number
US07338947B2

Reaction notes

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