Dimethylformamide → 4-Chloro-8-methoxy-2-(trifluoromethyl)quinoline

HRID 323001Notes

Reaction equation

HRID 323001 reaction equation
O[C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=1.CN(C=O)C.O=P(Cl)(Cl)[Cl:25]>C(Cl)Cl>[Cl:25][C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 178488807HCID 178488807, compound

Product 1

HCID 6215244-Chloro-8-methoxy-2-(trifluoromethyl)quinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Hydroxy-8-methoxy-2-trifluoromethylquinoline (18.77 g) is dissolved in 450 mL 8:1 CH2Cl2:DMF. POCl3 (50 mL) is added dropwise and the reaction is allowed to stir overnight. The reaction is then poured into 500 mL ice/H2O and the aqueous is extracted 2× with CH2Cl2. The organic portions are combined, washed 1× with brine, dried over MgSO4, and evaporated. The resulting oil crystallizes upon standing. The solid is recrystallized from 95% EtOH. A second crop of crystals could be obtained by concentrating down the EtOH filtrate. The total yield of product is 15.36 g.

Workup

  1. extractionthe aqueous is extracted 2× with CH2Cl2
  2. washwashed 1× with brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe resulting oil crystallizes
  6. customThe solid is recrystallized from 95% EtOH
  7. customA second crop of crystals could be obtained
  8. concentrationby concentrating down the EtOH filtrate

Sources & evidence

ORD record
ord-67cb2e9ad07a4d229e54d025d3bd1654
Source dataset
uspto-grants-2001_04
Patent number
US06211376B1

Reaction notes

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