Trifluoroacetic acid → HCID 136102864, compound

HRID 1710149Notes

Reaction equation

HRID 1710149 reaction equation
C([Li])CCC.[CH:6]([NH:9]C(C)C)(C)C.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH:23]2CN(OC)[C:26]3=[CH:27][O:28][CH:29]=[C:25]3[CH2:24]2)[CH:18]=[CH:19][C:20]=1[O:21][CH3:22].[CH3:34][O:35][C:36]([C:38]#[C:39][C:40]([O:42][CH3:43])=[O:41])=[O:37].FC(F)(F)C(O)=O>CCCCCC.O1CCCC1.C1C=CC=CC=1.O.C(O)(=O)C>[OH:28][C:29]1[C:38]([C:36]([O:35][CH3:34])=[O:37])=[C:39]([C:40]([O:42][CH3:43])=[O:41])[C:23]([C:17]2[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:15]([O:14][CH3:13])[CH:16]=2)=[C:24]2[C:25]=1[CH:26]=[CH:27][CH:6]=[N:9]2

Participants

11

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7912DiisopropylamineHCID 12980Dimethyl acetylenedicarboxylateHCID 70359732HCID 70359732, compoundHCID 178418339Butyllithium

Product 1

HCID 136102864HCID 136102864, compoundYield 18.9%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolvent2×HCID 241BenzeneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

45 ml of 1.55M n-butyl lithium in hexane are added at a temperature of -70° to -50° C. to a solution of 7.0 g of diisopropylamine in 100 ml of tetrahydrofuran. The mixture is stirred for 30 minutes at a temperature of 0° to 10° C., and then chilled to -70° C. Further, a solution of 5.0 g of 3-(3,4-dimethoxyphenyl)-1-methoxy-1H,3H-pyridino[2,3-c]furan in 20 ml of tetrahydrofuran is added thereto for 10 minutes, and the mixture is stirred at the same temperature for 10 minutes. A solution of 4.2 g of acetic acid and 2.7 g of acetylenedicarboxylic acid dimethyl ester in 20 ml of tetrahydrofuran are added further thereto. The mixture is stirred at the same temperature for 10 minutes. A solution of 4.2 g of acetic acid in 10 ml tetrahydrofuran is added to the mixture at room temperature, and the mixture is stirred for 10 minutes. The reaction mixture is poured into 300 ml of water and extracted with ethyl acetate. The extract is dried and evaporated to remove the solvent. The residue is purified by silica gel column chromatography [solvent: hexane-ethyl acetate (1:2)], and the eluate is evaporated under reduced pressure to remove the solvent, whereby 1.8 g of pale brown oil are obtained. Said oil is dissolved in benzene, and 1.6 g of trifluoroacetic acid are added to the solution. The mixture is stirred at room temperature for one hour, and evaporated under reduced pressure to remove the solvent. 100 ml of ethyl acetate is added to the residue, and the mixture is neutralized with 100 ml of aqueous saturated sodium bicarbonate solution. The organic layer is dried and evaporated under reduced pressure to remove the solvent. The resulting pale brown crystals are washed with ether to give 1.3 g of 5-hydroxy-6,7-bis(methoxycarbonyl)-8-(3,4-dimethoxyphenyl)quinoline.

Workup

  1. waitfor 10 minutes
  2. stirringthe mixture is stirred at the same temperature for 10 minutes
  3. stirringThe mixture is stirred at the same temperature for 10 minutes
  4. stirringthe mixture is stirred for 10 minutes
  5. extractionextracted with ethyl acetate
  6. customThe extract is dried
  7. customevaporated
  8. customto remove the solvent
  9. customThe residue is purified by silica gel column chromatography [solvent: hexane-ethyl acetate (1:2)]
  10. customthe eluate is evaporated under reduced pressure
  11. customto remove the solvent, whereby 1.8 g of pale brown oil
  12. customare obtained
  13. stirringThe mixture is stirred at room temperature for one hour
  14. customevaporated under reduced pressure
  15. customto remove the solvent
  16. addition100 ml of ethyl acetate is added to the residue
  17. customThe organic layer is dried
  18. customevaporated under reduced pressure
  19. customto remove the solvent
  20. washThe resulting pale brown crystals are washed with ether

Sources & evidence

ORD record
ord-0120fbc5cd4d42c59285d0a591ae4336
Source dataset
uspto-grants-1990_08
Patent number
US04952602

Reaction notes

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