Sodium hydride → HCID 22222518, compound

HRID 1794641Notes

Reaction equation

HRID 1794641 reaction equation
[H-].[Na+].[CH3:3][C:4]1[C:13]([CH3:14])=[C:12]([OH:15])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:20])[C:10]=2[C:16]([F:19])([F:18])[F:17])[N:5]=1.C(C1C(C)=C([O:34][C:35]([CH:37]2[CH2:39][CH2:38]2)=O)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>[CH3:3][C:4]1[C:13]([CH3:14])=[C:12]([O:15][C:35]([CH:37]2[CH2:39][CH2:38]2)=[O:34])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:20])[C:10]=2[C:16]([F:17])([F:19])[F:18])[N:5]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 9857197HCID 9857197, compound2×HCID 22222485HCID 22222485, compound2×HCID 178432189HCID 178432189, compound

Product 1

HCID 22222518HCID 22222518, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

In 3 ml dimethyl formamide was suspended 18.8 mg of 60% sodium hydride. The mixture of 2,3-dimethyl-4-hydroxy-5-trifluoromethyl-6-fluoroquinoline with 2,3-dimethyl-4-hydroxy-6-fluoro-7-trifluoromethylquinoline (starting material 1) (100 mg) was suspended in 3 ml of dimethyl formamide, and this suspension was added dropwise to the above suspension under ice cooling. After stirring for one hr, 40.8 mg of cyclopropanecarbonyl 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 a silica gel packed column (Varian) (20 g; elution solvent=n-hexane-ethyl acetate (40:1) to (20:1)) to give 27.9 mg of 2,3-dimethyl-4-cyclopropanecarbonyloxy-5-trifluoromethyl-6-fluoroquinoline (compound 61) and 51.3 mg of 2,3-dimethyl-4-cyclopropanecarbonyloxy-6-fluoro-7-trifluoro -methylquinoline (compound 63). 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 a silica gel
  9. washcolumn (Varian) (20 g; elution solvent=n-hexane-ethyl acetate (40:1) to (20:1))

Sources & evidence

ORD record
ord-39d3294dcbe1439d8ab87235590fb034
Source dataset
uspto-grants-2006_04
Patent number
US07022855B2

Reaction notes

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