Water → HCID 9964906, compound

HRID 1794640Notes

Reaction equation

HRID 1794640 reaction equation
[H-].[Na+].C(C1C(C)=C(OC(C2CC2)=O)C2C(=CC(F)=C(F)C=2)N=1)C.[CH2:24]([C:26]1[C:35]([CH3:36])=[C:34]([O:37][C:38]([CH:40]2CC2)=[O:39])[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:44])[C:32]=2[F:43])[N:27]=1)C.O>CN(C)C=O>[CH3:24][C:26]1[C:35]([CH3:36])=[C:34]([O:37][C:38](=[O:39])[CH3:40])[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:44])[C:32]=2[F:43])[N:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 9857197HCID 9857197, compound2×HCID 22222485HCID 22222485, compound2×

Product 1

HCID 9964906HCID 9964906, compoundYield 314.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,3-Dimethyl-4-cyclopropanecarbonyloxy-5,6-difluoroquinoline (1.5 g) prepared as described in Example 4 was dissolved in 15 ml of methanol. A 10% aqueous sodium hydroxide solution (15 ml) was added to the solution, and the mixture was stirred at 50° C. for 1.5 hr. The reaction mixture was allowed to stand for cooling, was then poured into 50 ml of water, and was neutralized with 1 N hydrochloric acid, and the precipitate was then collected by filtration to give 1.1 g of 2,3-dimethyl-4-hydroxy-5,6-difluoroquinoline. In 5 ml of dimethyl formamide was suspended 11.5 mg of 60% sodium hydride. Separately, 50 mg of 2,3-dimethyl-4-hydroxy-5,6-difluoroquinoline (starting material 1) prepared above was suspended in 5 ml of dimethyl formamide, and this suspension was added dropwise to the above suspension under ice cooling. After stirring for one hr, 20 mg of acetyl chloride (starting material 2) was added thereto, and the mixture was stirred at room temperature for 15 hr. The reaction solution was poured into water, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine and was then dried over anhydrous sodium sulfate. The solvent was then removed by evaporation under the reduced pressure. The crude product thus obtained was purified on Wako Gel C-200 (100 ml; elution solvent=n-hexane-ethyl acetate (10:1)) to give 54.2 mg of 2,3-dimethyl-4-acetoxy-5,6-difluoroquinoline (compound 44). 1H-NMR data are shown in Table 3.

Workup

  1. additionthis suspension was added dropwise to the above suspension under ice cooling
  2. stirringthe mixture was stirred at room temperature for 15 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine
  5. dry with materialwas then dried over anhydrous sodium sulfate
  6. customThe solvent was then removed by evaporation under the reduced pressure
  7. customThe crude product thus obtained
  8. customwas purified on Wako Gel
  9. wash(100 ml; elution solvent=n-hexane-ethyl acetate (10:1))

Sources & evidence

ORD record
ord-8771f010c8aa4df0b7cccd875479e4f6
Source dataset
uspto-grants-2006_04
Patent number
US07022855B2

Reaction notes

Loading…