3-Aminoquinoline → Ethyl (+/-)-4-(4,4,4-trifluoro-1-(quinolin-3-ylamino)butyl)benzoate

HRID 2281153Notes

Reaction equation

HRID 2281153 reaction equation
[F:1][C:2]([F:23])([F:22])[CH2:3][CH2:4][CH:5]([C:11]1[CH:21]=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][CH:12]=1)OS(C)(=O)=O.[NH2:24][C:25]1[CH:26]=[N:27][C:28]2[C:33]([CH:34]=1)=[CH:32][CH:31]=[CH:30][CH:29]=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.O>[F:1][C:2]([F:23])([F:22])[CH2:3][CH2:4][CH:5]([C:11]1[CH:21]=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][CH:12]=1)[NH:24][C:25]1[CH:26]=[N:27][C:28]2[C:33]([CH:34]=1)=[CH:32][CH:31]=[CH:30][CH:29]=2

Participants

6

Reactant 3

HCID 113753-AminoquinolineHCID 62657Potassium Phosphate, TribasicHCID 86718838Ethyl(+/-)-4-(4,4,4-trifluoro-1-((methylsulfonyl)oxy)butyl)benzoate

Product 1

HCID 86718839Ethyl (+/-)-4-(4,4,4-trifluoro-1-(quinolin-3-ylamino)butyl)benzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl (+/−)-4-(4,4,4-trifluoro-1-((methylsulfonyl)oxy)butyl)benzoate (123 mg, 0.347 mmol) in acetonitrile (1.74 mL) was added 3-amino quinoline (60.6 mg, 0.416 mmol), followed by potassium phosphate (155 mg, 0.694 mmol). The resulting mixture was heated to 60° C. for 20 hours. The reaction mixture was cooled to room temperature, diluted with water (20 mL), and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave ethyl (+/−)-4-(4,4,4-trifluoro-1-(quinolin-3-ylamino)butyl)benzoate. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=2.5 Hz, 1H), 8.06 (d, J=8.4 Hz, 2 H), 7.92 (d, J=7.8 Hz, 1 H), 7.50-7.44 (m, 3 H), 7.44-7.35 (m, 2 H), 6.81 (d, J=2.5 Hz, 1 H), 4.62-4.54 (m, 1 H), 4.44-4.33 (m, 3 H), 2.36-2.10 (m, 4 H), 1.38 (t, J=7.1 Hz, 3 H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-b41f2a3a7aa94360abe6e1173ae58a52
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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