Pivalic acid → 6-Hydroxy-2,5-quinolinedipropanoic Acid Diethyl Ester

HRID 1648109Notes

Reaction equation

HRID 1648109 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:17])[CH:13]=2)[N:8]=1)[CH3:2].CCC(CC)=[C:22]([C:25]([O-:28])([O-:27])[O-])[CH2:23]C.[CH3:31][C:32](C)(C)C(O)=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CCOCC.C(OCC)(=O)C.O>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:13]([CH2:23][CH2:22][C:25]([O:27][CH2:31][CH3:32])=[O:28])=[C:12]([OH:17])[CH:11]=[CH:10][C:9]=2[N:8]=1)[CH3:2]

Participants

10

Reactant 5

HCID 6417Pivalic acidHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 19600934Triethyl orthoacrylate2×HCID 544101086-Hydroxy-2-quinolinepropanoic Acid Ethyl Ester

Product 1

HCID 536708086-Hydroxy-2,5-quinolinedipropanoic Acid Diethyl EsterYield 83%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.779 g (3.17 mmol) of 6-hydroxy-2-quinolinepropanoic acid ethyl ester from the preceding example, 1.11 g (6.38 mmol) of triethyl orthoacrylate and 0.491 g (4.81 mmol) of trimethylacetic acid in 21 mL of toluene was stirred at reflux for 16 hr. A solution of 0.283 g (1.62 mmol) of triethyl orthoacrylate in 3 mL of toluene was added and the reaction was allowed to stir under reflux for another 23 hr. After being cooled to room temperature, the solution was diluted with ether, washed three times with saturated aqueous sodium bicarbonate, and work-up was completed in the usual manner. To the residue was added 25 mL of ether, 25 mL of water and 1.21 g (6.36 mmol) of p-toluenesulfonic acid monohydrate and the resulting mixture was stirred at room temperature for 1.5 hr. Saturated aqueous sodium bicarbonate was added and the mixture was worked-up with ethyl acetate in the usual manner. The crude product was flash chromatographed on 110 g of silica gel, eluting with hexane-ethyl acetate (3:1 and 2:1) affording 0.909 g (82.9%) of the title compound as a white solid, mp 74°-76° C.

Workup

  1. temperatureat reflux for 16 hr
  2. temperatureunder reflux for another 23 hr
  3. washwashed three times with saturated aqueous sodium bicarbonate
  4. stirringthe resulting mixture was stirred at room temperature for 1.5 hr
  5. customchromatographed on 110 g of silica gel
  6. washeluting with hexane-ethyl acetate (3:1 and 2:1)

Sources & evidence

ORD record
ord-f7e91c2aa4a4450d8a49787bd1bb9a49
Source dataset
uspto-grants-1995_07
Patent number
US05434186

Reaction notes

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