2-Hydroxyquinoline → HCID 69737188, compound

HRID 897215Notes

Reaction equation

HRID 897215 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:7](=[O:17])[CH:6]=[C:5]2O.[H-].[Na+].FC(F)(F)S(N(C1C=CC=CC=1)S(C(F)(F)F)(=O)=O)(=O)=O.N1C2C(=CC=CC=2)C=CC1=O.[CH2:53]([O:55][C:56]([N:58]1[CH2:63][CH2:62][CH:61]([NH2:64])[CH2:60][CH2:59]1)=[O:57])[CH3:54]>C(#N)C>[CH2:53]([O:55][C:56]([N:58]1[CH2:59][CH2:60][CH:61]([NH:64][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=3)[N:8]([CH2:12][C:13]([F:16])([F:15])[F:14])[C:7](=[O:17])[CH:6]=2)[CH2:62][CH2:63]1)=[O:57])[CH3:54]

Participants

7

Reactant 5

HCID 60382-HydroxyquinolineHCID 24758Sodium hydrideHCID 100867Ethyl 4-amino-1-piperidinecarboxylateHCID 142176Phenyl triflimideHCID 54697738HCID 54697738, compound

Product 1

HCID 69737188HCID 69737188, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

6-Chloro-4-hydroxy-1-(2,2,2-trifluoroethyl)-1H-quinolin-2-one (0.996 g, 3.6 mmol) was suspended in dry acetonitrile (50 mL) under argon and treated with sodium hydride (0.16 g, 60% wt in mineral oil, 4 mmol). After stirring for 10 minutes, 1,1,1-trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide (1.36 g, 3.8 mmol) was added and the mixture heated to 50° C. for 6 hours. Analysis by LC/MS indicated the starting quinolone had been completely consumed and 4-aminopiperidine-1-carboxylic acid ethyl ester (770 μL, 4.5 mmol) was added. The reaction was heated to reflux for 18 hours at which time LC/MS analysis indicated complete consumption of the intermediate triflate. The solution was diluted with ethyl acetate and washed with 1 N NaOH. The organic layer was dried with sodium sulfate and concentrated under reduced pressure to give the crude product. This material was purified by silica chromatography using DCM and methanol eluent gave the title compound (0.91 g). 1H NMR (300 MHz, CDCl3) δ ppm 1.31 (5H, t, J=7.03 Hz), 2.02 (2H, m), 2.85 (2H, m), 3.50 (1H, m), 4.05 (2H, q, J=7.02 Hz), 4.80-5.11 (4H, m), 5.78 (1H, s), 7.28 (2H, m), 7.52 (2H, m).

Workup

  1. customhad been completely consumed
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 18 hours at which time LC/MS analysis
  4. customconsumption of the intermediate triflate
  5. additionThe solution was diluted with ethyl acetate
  6. washwashed with 1 N NaOH
  7. dry with materialThe organic layer was dried with sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product
  10. customThis material was purified by silica chromatography

Sources & evidence

ORD record
ord-6c984f74cae042459e890fec25d475c5
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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