Sodium hydride → HCID 22222472, compound

HRID 1794634Notes

Reaction equation

HRID 1794634 reaction equation
[H-].[Na+].[CH2:3]([C:5]1[C:14]([CH3:15])=[C:13]([OH:16])[C:12]2[C:7](=[CH:8][C:9]([Cl:18])=[C:10]([F:17])[CH:11]=2)[N:6]=1)[CH3:4].C(C1C(C)=C([O:32][C:33]([CH:35]2[CH2:37][CH2:36]2)=O)C2C(=CC(F)=C(F)C=2)N=1)C.[CH2:40]([C:42]1[C:51]([CH3:52])=[C:50]([O:53][C:54]([CH:56]2[CH2:58][CH2:57]2)=[O:55])[C:49]2[C:44](=[CH:45][CH:46]=[C:47]([F:60])[C:48]=2F)[N:43]=1)[CH3:41]>O1CCCC1.O>[CH2:3]([C:5]1[C:14]([CH3:15])=[C:13]([O:16][C:33]([CH:35]2[CH2:37][CH2:36]2)=[O:32])[C:12]2[C:7](=[CH:8][C:9]([Cl:18])=[C:10]([F:17])[CH:11]=2)[N:6]=1)[CH3:4].[CH2:40]([C:42]1[C:51]([CH3:52])=[C:50]([O:53][C:54]([CH:56]2[CH2:58][CH2:57]2)=[O:55])[C:49]2[C:44](=[CH:45][CH:46]=[C:47]([F:60])[C:48]=2[Cl:18])[N:43]=1)[CH3:41]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 9857197HCID 9857197, compound2×HCID 22222485HCID 22222485, compound2×HCID 178437472HCID 178437472, compound

Product 2

HCID 22222472HCID 22222472, compoundHCID 22222479HCID 22222479, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In 5 ml of tetrahydrofuran was suspended 90.3 mg of 60% sodium hydride. Separately, 400 mg of the mixture of 2-ethyl-3-methyl-4-hydroxy-6-fluoro-7-chloroquinoline with 2-ethyl-3-methyl-4-hydroxy-5-chloro-6-fluoroquinoline (starting material 1) prepared as described in Example 6 was suspended in 10 ml of tetrahydrofuran, and this suspension was added dropwise to the above suspension under ice cooling. The mixture was stirred for one hr. Cyclopropanecarbonyl chloride (starting material 2) (240 mg) was then 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, and the solvent was then removed by evaporation under the reduced pressure. The crude product thus obtained was purified on Wako Gel C-200 (200 ml; elution solvent=n-hexane-ethyl acetate (10:1)) to give 245.4 mg of 2-ethyl-3-methyl-4-cyclopropanecarbonyloxy-6-fluoro-7-chloroquinoline (compound 20) and 129.2 mg of 2-ethyl-3-methyl-4-cyclopropanecarbonyloxy-5-chloro-6-fluoroquinoline (compound 21). 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(200 ml; elution solvent=n-hexane-ethyl acetate (10:1))

Sources & evidence

ORD record
ord-2a7cee9eb750463f98d0c85111664ff0
Source dataset
uspto-grants-2006_04
Patent number
US07022855B2

Reaction notes

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