Tetrahydrofuran → (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid ethyl ester

HRID 1063481Notes

Reaction equation

HRID 1063481 reaction equation
[H-].[Na+].O1CCCC1.[CH2:8]([O:10][C:11](=[O:19])[CH2:12][C:13](=[O:18])[CH2:14][C:15](=[O:17])[CH3:16])[CH3:9].[CH:20]1([C:23]2[C:32]([CH:33]=O)=[C:31]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)[CH2:22][CH2:21]1>C(O)(=O)C>[CH2:8]([O:10][C:11](=[O:19])[CH2:12][C:13](=[O:18])[CH2:14][C:15](=[O:17])/[CH:16]=[CH:33]/[C:32]1[C:23]([CH:20]2[CH2:21][CH2:22]2)=[N:24][C:25]2[C:30]([C:31]=1[C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH3:9]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 24758Sodium hydrideHCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehydeHCID 11332732Ethyl 3,5-dioxohexanoate

Product 1

HCID 11362810(E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid ethyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In a mixture solution of 1.37 g of an oily 60% sodium hydride and 10 ml of tetrahydrofuran, a mixture solution of 2.36 g of 3,5-dioxohexanoic acid ethyl ester and 10 ml of tetrahydrofuran was dropped in 5 minutes while keeping an inner temperature of 20° C. After stirring the mixture for 1 hour at that temperature, a mixture of 2.01 g of 2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-carbaldehyde and 20 ml of tetrahydrofuran was dropped for 20 minutes. After stirring the mixture for 4 hours, a reaction solution was added in 3.09 g of acetic acid and 20 ml of water to terminate the reaction. An organic phase was extracted with 40 ml of ethyl acetate and was then washed with 20 ml of saturated brine, followed by being dried with 2 g of anhydrous sodium sulfate. As a result of analysis on the resulting organic phase, 2.52 g of (E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dioxohept-6-enic acid ethyl ester (DOXE) (yield 82%) was obtained.

Workup

  1. customan inner temperature of 20° C
  2. additionwas dropped for 20 minutes
  3. stirringAfter stirring the mixture for 4 hours
  4. custom20 ml of water to terminate
  5. customthe reaction
  6. extractionAn organic phase was extracted with 40 ml of ethyl acetate
  7. washwas then washed with 20 ml of saturated brine
  8. dry with materialby being dried with 2 g of anhydrous sodium sulfate
  9. customAs a result of analysis on the resulting organic phase

Sources & evidence

ORD record
ord-54ebc5bc0ad04270b4756ad50340e743
Source dataset
uspto-grants-2005_11
Patent number
US06965031B2

Reaction notes

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