Trifluoroacetic acid → ethyl (2E)-3-(7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinolin-4-yl)acrylate

HRID 39761Notes

Reaction equation

HRID 39761 reaction equation
[O:1]1CCO[CH:2]1[CH2:6][N:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[C:10](/[CH:19]=[CH:20]/[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:9][C:8]1=[O:26].FC(F)(F)C(O)=O>>[CH3:18][O:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10](/[CH:19]=[CH:20]/[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:9][C:8](=[O:26])[N:7]2[CH2:6][CH:2]=[O:1])=[CH:12][CH:13]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59398090HCID 59398090, compound

Product 1

HCID 59397901ethyl (2E)-3-(7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinolin-4-yl)acrylateYield 59.8%

Procedure

To 0.16 g of ethyl (2E)-3-(1-(1,3-dioxolan-2-ylmethyl)-7-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)acrylate, 2 mL of 90% aqueous trifluoroacetic acid solution was added and stirred for 2 hours. The solvent was removed under reduced pressure, and aqueous saturated sodium hydrogen carbonate solution and chloroform were added. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and extracts were combined, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (eluent; chloroform) to give 84 mg of ethyl (2E)-3-(7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinolin-4-yl)acrylate as a yellow oil. (2) To 3 mL of a dichloromethane solution containing 84 mg of ethyl (2E)-3-(7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinolin-4-yl)acrylate, 98 mg of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamate and 14 μL of acetic acid were added and stirred for 1 hour. To the reaction mixture, 81 mg of sodium triacetoxyborohydride was added and stirred for 2 hours. Water, ethyl acetate and aqueous saturated sodium hydrogen carbonate solution were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and extracts were combined, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; chloroform:methanol=100:1] to give 0.11 g of ethyl (2E)-3-(1-(2-(4-((tert-butoxycarbonyl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)acrylate as a yellow oil.

Workup

  1. customThe solvent was removed under reduced pressure, and aqueous saturated sodium hydrogen carbonate solution and chloroform
  2. additionwere added
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with chloroform
  5. washwashed with aqueous saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by silica gel column chromatography (eluent; chloroform)

Sources & evidence

ORD record
ord-9d3b98ceace148f78871140088840085
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Reaction notes

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