Triethylamine → 2-[(8-Difluoromethoxyquinolin-5-yl)carbonyl]-4,4,6,6-tetramethylcyclohexane-1,3,5-trione

HRID 1795753Notes

Reaction equation

HRID 1795753 reaction equation
[F:1][CH:2]([F:17])[O:3][C:4]1[C:13]2[N:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:7]([C:14]([OH:16])=O)=[CH:6][CH:5]=1.[CH3:18][C:19]1([CH3:30])[C:24](=[O:25])[C:23]([CH3:27])([CH3:26])[C:22](=[O:28])[CH2:21][C:20]1=[O:29].C(N(CC)CC)C>C(#N)C.C[Si](C#N)(C)C>[F:17][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:14]([CH:21]2[C:20](=[O:29])[C:19]([CH3:30])([CH3:18])[C:24](=[O:25])[C:23]([CH3:27])([CH3:26])[C:22]2=[O:28])=[O:16])=[C:8]2[C:13]=1[N:12]=[CH:11][CH:10]=[CH:9]2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 117691662,2,4,4-Tetramethylcyclohexane-1,3,5-trioneHCID 221791908-Difluoromethoxy-5-quinolinecarboxylic acid

Product 1

HCID 221791792-[(8-Difluoromethoxyquinolin-5-yl)carbonyl]-4,4,6,6-tetramethylcyclohexane-1,3,5-trione

Reagents, catalysts & solvents 2

HCID 82115Trimethylsilyl cyanideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

0.4 g (1.7 mmol) of 8-difluoromethoxy-5-quinolinecarboxylic acid was dissolved in 20 ml of acetonitrile, 0.4 g (1.9 mmol) of N,N-dicyclohexylcarbodiimide and 0.3 g (1.7 mmol) of 2,2,4,4-tetramethylcyclohexane-1,3,5-trione were added and the mixture was stirring at 25° C. for 20 hours. 0.4 g (4.0 mmol) of triethylamine and 2 drops of trimethylsilyl cyanide were then added, and stirring was continued at 30–35° C. for a further 3 hours. The precipitate was filtered off, and the filtrate was concentrated, 20 ml of 5% strength potassium carbonate solution were added and the mixture was washed with methyl tert-butyl ether. The aqueous phase was subsequently adjusted to pH 3 using concentrated hydrochloric acid and extracted with ethyl acetate. The solvent was removed and the residue was chromatographed over silica gel (mobile phase: methylene chloride/methanol). This gave 0.2 g of a colorless powder;

Workup

  1. stirringstirring
  2. waitwas continued at 30–35° C. for a further 3 hours
  3. filtrationThe precipitate was filtered off
  4. concentrationthe filtrate was concentrated
  5. addition20 ml of 5% strength potassium carbonate solution were added
  6. washthe mixture was washed with methyl tert-butyl ether
  7. extractionextracted with ethyl acetate
  8. customThe solvent was removed
  9. customthe residue was chromatographed over silica gel (mobile phase: methylene chloride/methanol)

Sources & evidence

ORD record
ord-0d8b37eaa90146c9a1e1735757c7949d
Source dataset
uspto-grants-2006_04
Patent number
US07030063B1

Reaction notes

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