Sodium hydride → HCID 22222506, compound

HRID 1794638Notes

Reaction equation

HRID 1794638 reaction equation
[CH2:1]([C:3]1[C:12]([CH3:13])=[C:11]([OH:14])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([F:16])[C:9]=2[Cl:15])[N:4]=1)[CH3:2].[H-].[Na+].C(C1C(C)=[C:29]([O:32][C:33](C2CC2)=[O:34])C2C(=CC(F)=C(F)C=2)N=1)C.C(C1C(C)=C(OC(C2CC2)=O)C2C(=CC=C(F)C=2F)N=1)C>CN(C)C=O.O>[CH2:1]([C:3]1[C:12]([CH3:13])=[C:11]([O:14][C:33]([O:32][CH3:29])=[O:34])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([F:16])[C:9]=2[Cl:15])[N:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 9857197HCID 9857197, compound2×HCID 22222485HCID 22222485, compound2×HCID 178437466HCID 178437466, compound

Product 1

HCID 22222506HCID 22222506, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

2-Ethyl-3-methyl-4-cyclopropanecarbonyloxy-5-chloro-6-fluoroquinoline (1.5 g) prepared as described in Example 7 was dissolved in 70 ml of methanol. To this solution was added 30 ml of a 10% aqueous sodium hydroxide solution. 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 1.17 g of 0.2-ethyl-3-methyl-4-hydroxy-5-chloro-6-fluoroquinoline. In 15 ml of dimethyl formamide was suspended 40.1 mg of 60% sodium hydride. Separately, 200 mg of 2-ethyl-3-methyl-4-hydroxy-5-chloro-6-fluoroquinoline (starting material 1) prepared above was suspended in 2 ml of dimethyl formamide, and this suspension was added dropwise to the above suspension under ice cooling. After stirring for one hr, 78.5 mg of methyl chloroformate (starting material 2) was added thereto, and the mixture was stirred at room temperature for 3 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 218.8 mg of 2-ethyl-3-methyl-4-methoxycarbonyloxy-5-chloro-6-fluoroquinoline (compound 36). 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 3 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution
  5. dry with materialsaturated, brine and was 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-7bd1998efd1f42d692452209fcc500e5
Source dataset
uspto-grants-2006_04
Patent number
US07022855B2

Reaction notes

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