Water → HCID 22222477, compound

HRID 1794635Notes

Reaction equation

HRID 1794635 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].[CH2:19]([C:21]1[C:30]([CH3:31])=[C:29]([O:32][C:33](C2CC2)=[O:34])[C:28]2[C:23](=[CH:24][C:25](F)=[C:26]([F:38])[CH:27]=2)[N:22]=1)[CH3:20].C(C1[C:51](C)=[C:50]([O:53][C:54](C2CC2)=[O:55])[C:49]2C(=CC=C(F)C=2F)N=1)C.[OH2:61]>O1CCCC1>[CH2:3]([C:5]1[C:14]([CH3:15])=[C:13]([O:16][C:33]([O:32][CH:29]([CH3:30])[CH3:28])=[O:34])[C:12]2[C:7](=[CH:8][C:9]([Cl:18])=[C:10]([F:17])[CH:11]=2)[N:6]=1)[CH3:4].[CH2:19]([C:21]1[C:30]([CH3:31])=[C:29]([O:61][C:54]([O:53][CH:50]([CH3:51])[CH3:49])=[O:55])[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:38])[C:27]=2[Cl:18])[N:22]=1)[CH3:20]

Participants

8

Reactant 5

HCID 962WaterHCID 24758Sodium hydrideHCID 9857197HCID 9857197, compound2×HCID 22222485HCID 22222485, compound2×HCID 178437472HCID 178437472, compound

Product 2

HCID 22222477HCID 22222477, compoundHCID 22222533HCID 22222533, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In ml of tetrahydrofuran was suspended 96 mg of 60% sodium hydride. 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) (480 mg) 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. After stirring for one hr, 300 mg of isopropyl chloroformate (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 (200 ml; elution solvent=n-hexane-ethyl acetate (10:1)) to give 345.1 mg of 2-ethyl-3-methyl-4-isopropoxycarbonyloxy-6-fluoro-7-chloroquinoline (compound 22) and 170.7 mg of 2-ethyl-3-methyl-4-isopropoxycarbonyloxy-5-chloro-6-fluoro -quinoline (compound 23). 1H-NMR data are shown in Table 3.

Workup

  1. customprepared
  2. additionthis suspension was added dropwise to the above suspension under ice cooling
  3. stirringthe mixture was stirred at room temperature for 15 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine
  6. dry with materialwas then dried over anhydrous sodium sulfate
  7. customThe solvent was then removed by evaporation under the reduced pressure
  8. customThe crude product thus obtained
  9. customwas purified on Wako Gel
  10. wash(200 ml; elution solvent=n-hexane-ethyl acetate (10:1))

Sources & evidence

ORD record
ord-8b824e212b134e3a8a96087bbc9118ee
Source dataset
uspto-grants-2006_04
Patent number
US07022855B2

Reaction notes

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