Dimethyl Sulfate → HCID 59710983, compound

HRID 2376800Notes

Reaction equation

HRID 2376800 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15]([NH:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[C:23]([C:28]([OH:30])=[O:29])[CH:24]=4)[N:19]=3)=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.[C:33]([O-])([O-])=O.[K+].[K+].[OH-].[K+].COS(OC)(=O)=O>C1(C)C=CC=CC=1.[N+](CCCC)(CCCC)(CCCC)CCCC.[O-]S(O)(=O)=O>[CH3:33][N:17]([C:15]([C:10]1[C:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:31])[F:32])=[CH:8][CH:7]=2)=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:16])[C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]([OH:30])=[O:29])[CH:24]=2)[N:19]=1

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 597109732-[[[4′-(Trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]-6-quinolinecarboxylic acid

Product 1

HCID 59710983HCID 59710983, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid (F-1a2, 200 mg, 0.46 mM) in toluene (3.0 mL) was added Bu4NHSO4 (15.6 mg, 0.046 mM) and freshly powdered K2CO3 (127 mg, 0.92 mM), and KOH (128 mg, 2.28 mM). The resulting suspension was stirred at room temperature for 1 h. The mixture was heated to 70° C. and (CH3)2SO4 (95 uL, 1.01 mM) was added dropwise. The mixture was stirred at 70° C. for 2 h. LC/MS analysis revealed the residue to be a mixture of the acid F-1b2 and the corresponding methyl ester. After cooling to room temperature the mixture was concentrated and the residue was taken up in 5 mL of THF/methanol/H2O (3:1:1) and the resulting mixture was stirred until the methyl ester had been completely consumed (2 h). The mixture was diluted with H2O (5 mL) and the pH was adjusted to 2.0 with 1 N HCl. The mixture was extracted 3 times with EtOAc. The combined EtOAc fractions were dried (MgSO4), filtered and concentrated to provide F-1b2 (180 mg) as a colorless solid.

Workup

  1. temperatureThe mixture was heated to 70° C.
  2. stirringThe mixture was stirred at 70° C. for 2 h
  3. additiona mixture of the acid F-1b2
  4. temperatureAfter cooling to room temperature the mixture
  5. concentrationwas concentrated
  6. stirringthe resulting mixture was stirred until the methyl ester
  7. customhad been completely consumed (2 h)
  8. additionThe mixture was diluted with H2O (5 mL)
  9. extractionThe mixture was extracted 3 times with EtOAc
  10. dry with materialThe combined EtOAc fractions were dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto provide F-1b2 (180 mg) as a colorless solid

Sources & evidence

ORD record
ord-eb4c6e8e7e7e42018215359e7eaa9a74
Source dataset
uspto-grants-2008_12
Patent number
US07468378B2

Reaction notes

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