Carbon Dioxide → Trifluoromethanesulfonic acid 7-benzyloxy-6-methoxy-quinolin-4-yl ester

HRID 705629Notes

Reaction equation

HRID 705629 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([OH:19])=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.C(=O)=O.[F:33][C:34]([F:40])([F:39])[S:35](Cl)(=[O:37])=[O:36]>CN(C)C1C=CN=CC=1.O.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][S:35]([C:34]([F:40])([F:39])[F:33])(=[O:37])=[O:36])=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 79372,6-LutidineHCID 79000Trifluoromethanesulfonyl chlorideHCID 178486758HCID 178486758, compound

Product 1

HCID 57810077Trifluoromethanesulfonic acid 7-benzyloxy-6-methoxy-quinolin-4-yl esterYield 83.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a dry 2 L RBF containing 7-benzyloxy-6-methoxyquinolin-4-ol (75.3 g, 267 mmol) was added DCM (1 L), 4-dimethylaminopyridine (3.28 g, 26.8 mmol) and 2,6-lutidine (62 mL, 534 mmol). The mixture was cooled to −20° C. by controlled addition of dry ice to an acetone bath. Trifluoromethanesulfonyl chloride (37 mL, 350 mmol) was added dropwise to the cooled solution with magnetic stirring over 25 minutes. After addition was complete, the mixture was stirred in bath for 20 minutes, then at room temperature for 3 hours. LCMS indicated reaction completion. The reaction mixture was concentrated in vacuo and placed under high vacuum to remove residual 2,6-lutidine. To the resulting brown solids was added methanol (3.5 L). The resulting slurry was stirred with mechanical stirrer for 30 min before adding water (1.5 L). The solids were isolated by filtration, followed by a water wash. The resulting solid was dried under high vacuum overnight yielding trifluoromethanesulfonic acid 7-benzyloxy-6-methoxy-quinolin-4-yl ester as a light brown solid (92.2 g, 83.8%). 1H NMR (400 MHz, DMSO, d6): δ 8.82 (d, 1H), 7.67 (s, 1H), 7.59 (d, 1H), 7.54-7.52 (m, 2H), 7.46-7.42 (m, 2H), 7.39-7.36 (m, 1H), 7.23 (s, 1H), 5.35 (s, 2H), 3.97 (s, 3H). LC/MS: M+H=414.

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred in bath for 20 minutes
  3. waitat room temperature for 3 hours
  4. customreaction completion
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customto remove residual 2,6-lutidine
  7. additionTo the resulting brown solids was added methanol (3.5 L)
  8. stirringThe resulting slurry was stirred with mechanical stirrer for 30 min
  9. additionbefore adding water (1.5 L)
  10. customThe solids were isolated by filtration
  11. washwash
  12. customThe resulting solid was dried under high vacuum overnight

Sources & evidence

ORD record
ord-99ff5b5aed3d47be823a7e4dd492510b
Source dataset
uspto-grants-2015_11
Patent number
US09174947B2

Reaction notes

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