Trifluoroacetic acid → 5-Oxo-2-trifluoromethyl-5,6,7,8-tetrahydro-quinoline-7-carboxylic acid methyl ester

HRID 2039631Notes

Reaction equation

HRID 2039631 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][C:9](=[O:11])[CH2:8][C:7](=O)[CH2:6]1)=[O:4].N/[CH:14]=[CH:15]\[C:16](=O)[C:17]([F:20])([F:19])[F:18].FC(F)(F)C(O)=O.FC(F)(F)C([O-])=O.[NH4+:36]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:6][C:7]2[N:36]=[C:16]([C:17]([F:20])([F:19])[F:18])[CH:15]=[CH:14][C:8]=2[C:9](=[O:11])[CH2:10]1)=[O:4]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 2724268Ammonium trifluoroacetateHCID 11019285Methyl 3,5-dioxocyclohexane-1-carboxylateHCID 11116141(Z)-4-amino-1,1,1-trifluorobut-3-en-2-one

Product 1

HCID 578559035-Oxo-2-trifluoromethyl-5,6,7,8-tetrahydro-quinoline-7-carboxylic acid methyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3,5-Dioxo-cyclohexanecarboxylic acid methyl ester (3.6 g, 21.16 mmol, preparation as in Journal of the Chemical Society, Perkin Transactions 1 (1976), (13), 1382-4), (Z)-4-Amino-1,1,1-trifluoro-but-3-en-2-one (2.94 g, 21.16 mmol, prepared as in EP 744400 (1996)), trifluoroacetic acid (1.21 g, 10.58 mmol), and ammonium trifluoroacetate (1.39 g, 10.58 mmol) in toluene (50 ml) are heated at reflux temperature in a Dean-Stark apparatus. After reaction completion, the reaction mixture is cooled, diluted with ethyl acetate and then washed successively with saturated aqueous sodium bicarbonate and water. The organic phase is dried over anhydrous sodium sulphate, filtered, and concentrated in vacuo. The residue is purified by flash chromatography, eluting with 4:1 hexane to give the title compound (1.5 g, 68%) as white crystals.

Workup

  1. temperatureare heated
  2. temperatureat reflux temperature in a Dean-Stark apparatus
  3. customAfter reaction completion
  4. temperaturethe reaction mixture is cooled
  5. washwashed successively with saturated aqueous sodium bicarbonate and water
  6. dry with materialThe organic phase is dried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by flash chromatography
  10. washeluting with 4:1 hexane

Sources & evidence

ORD record
ord-f07d11c916464953b4aa28af2c7874f0
Source dataset
uspto-grants-2013_11
Patent number
US08580785B2

Reaction notes

Loading…