Dichloromethane → Flometoquin

HRID 2273842Notes

Reaction equation

HRID 2273842 reaction equation
C(Cl)Cl.[CH2:4]([C:6]1[NH:7][C:8]2[C:13]([C:14](=[O:17])[C:15]=1[CH3:16])=[CH:12][C:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1)=[C:10]([CH3:30])[CH:9]=2)[CH3:5].[OH-].[Na+].Cl[C:34]([O:36][CH3:37])=[O:35]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CC(N(C)C)=O>[C:34](=[O:35])([O:36][CH3:37])[O:17][C:14]1[C:13]2[C:8](=[CH:9][C:10]([CH3:30])=[C:11]([O:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:27])([F:28])[F:29])=[CH:21][CH:20]=3)[CH:12]=2)[N:7]=[C:6]([CH2:4][CH3:5])[C:15]=1[CH3:16]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 6586Methyl chloroformateHCID 14798Sodium HydroxideHCID 67119408HCID 67119408, compound

Product 1

HCID 67119441FlometoquinYield 95.2%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Methylene chloride (1000 ml), 160 ml of dimethyl acetamide, 113.2 g of 2-ethyl-3,7-dimethyl-6-(4-(trifluoromethoxy)phenoxy)quinolin-4(1H)-one, and 4.8 g of tetrabutylammonium bromide were added to a glass vessel equipped with a stirring device, a thermometer, and a reflux condenser and having a volume of 3000 ml, and the mixture was stirred at room temperature. A 48% aqueous sodium hydroxide solution (50 g) was added dropwise at 25 to 30° C., and the mixture was stirred at the same temperature for one hr. After cooling to 10 to 15° C., 34 g of methyl chloroformate was added dropwise, and a reaction was allowed to proceed at the same temperature for one hr. Water was added to the reaction solution for washing. Methylene chloride was removed by evaporation, 990 ml of methanol was added to the residue, and the mixture was heated to dissolve the residue in methanol. Water (660 ml) was added dropwise thereto to precipitate crystals, and the precipitated solid was collected by a suction filter. The solid was dried in vacuo to give 2-ethyl-3,7-dimethyl-6-(4-(trifluoromethoxy)phenoxy)quinolin-4-yl methyl carbonate (124.4 g, yield 95.2%). It was confirmed from the results of measurement of 1H-NMR that the compound thus obtained was a compound of No. 120 described in WO2006/013896 (patent document 1).

Workup

  1. customequipped with a stirring device
  2. stirringthe mixture was stirred at the same temperature for one hr
  3. temperatureAfter cooling to 10 to 15° C.
  4. washfor washing
  5. customMethylene chloride was removed by evaporation, 990 ml of methanol
  6. additionwas added to the residue
  7. temperaturethe mixture was heated
  8. dissolutionto dissolve the residue in methanol
  9. additionWater (660 ml) was added dropwise
  10. customto precipitate crystals
  11. customthe precipitated solid was collected by a suction
  12. filtrationfilter
  13. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-8f15bcd9ad3d412794cbfbc98f9d4026
Source dataset
uspto-grants-2015_09
Patent number
US09126934B2

Reaction notes

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