Trifluoroacetic anhydride → 4-Chloro-6-methoxy-quinoline-3-carbonitrile

HRID 638970Notes

Reaction equation

HRID 638970 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH2:16])=O.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C(Cl)Cl.CCN(CC)CC>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]#[N:16]

Participants

5

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 221702744-Chloro-6-methoxyquinoline-3-carboxamide

Product 1

HCID 224667634-Chloro-6-methoxy-quinoline-3-carbonitrileYield 68%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a suspension of 4-chloro-6-(methyloxy)-3-quinolinecarboxamide (0.92 g, 3.9 mmol) in CH2Cl2 (8 mL) and Et3N (4 mL) at 0° C. was added TFAA (2.0 mL, 14 mmol) over 5 min. The reaction was warmed to rt and then stirred at this temperature for 2 h (complete by LCMS). The reaction solution was partitioned between water and CH2Cl2 and the organic phase was collected. The aqueous phase was further extracted with CH2Cl2. The organic layers were combined and washed with brine and dried over MgSO4. The solution was filtered and the solvent was removed in vacuo. The resulting material was redissolved in EtOAc and the product was precipitated via the addition of hexane. The solid material was collected by filtration and washed with cold hexanes and water to remove remaining Et3N. Isolated 580 mg (65%) of pure product as an off-white solid: LC/MS (ES) m/e 219 (M+H)+.

Workup

  1. customThe reaction solution was partitioned between water and CH2Cl2
  2. customthe organic phase was collected
  3. extractionThe aqueous phase was further extracted with CH2Cl2
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationThe solution was filtered
  7. customthe solvent was removed in vacuo
  8. dissolutionThe resulting material was redissolved in EtOAc
  9. customthe product was precipitated via the addition of hexane
  10. filtrationThe solid material was collected by filtration
  11. washwashed with cold hexanes and water
  12. customto remove

Sources & evidence

ORD record
ord-bd287612faf84cc19b4fe85cb646f832
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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