Dimethyl Sulfate → HCID 21834120, compound

HRID 1740872Notes

Reaction equation

HRID 1740872 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:5](=[O:26])[NH:6][C:7]2[C:12]([C:13]=1[C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[OH:21])=[CH:11][C:10]([C:22]([F:25])([F:24])[F:23])=[CH:9][CH:8]=2.[CH3:27]OCCl.S(OC)(OC)(=O)=O.B(Br)(Br)Br>[Cl-].[NH4+].CN(C=O)C>[Cl:20][C:18]1[CH:17]=[CH:16][C:15]([OH:21])=[C:14]([C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([C:22]([F:23])([F:25])[F:24])[CH:11]=3)[NH:6][C:5](=[O:26])[C:4]=2[NH:3][CH3:27])[CH:19]=1

Participants

8

Reactant 5

HCID 6497Dimethyl SulfateHCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydride2×HCID 25134Boron tribromideHCID 98415503-Amino-4-(5-chloro-2-hydroxyphenyl)-6-(trifluoromethyl)quinolin-2(1H)-one

Product 1

HCID 21834120HCID 21834120, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 25517Ammonium ChlorideSolvent2×

Procedure

Sodium hydride (1.3 g, 27.9 mmol) was added to a solution of 3-amino-4-(5-chloro-2-hydroxyphenyl)-6-(trifluoromethyl)quinolin-2(1H)-one (4.7 g, 13.3 mmol) and dry DMF at ambient temperature under nitrogen. Neat chloromethyl methyl ether was added and the reaction was stirred overnight. The reaction was then diluted with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. Chromatography on silica gel was used to isolated a mixture of O,N- and O,O-bis methoxymethyl quinolones (3.24 g) from remaining starting material. The bis methoxymethyl mixture was dissolved in dry DMF and sodium hydride(375.4 mg, 8 mmol) was added at ambient temperature under nitrogen. Dimethyl sulfate(0.76 ml, 8.0 mmol) was added and the reaction was stirred for 1 hour. The reaction mixture was then diluted with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The crude material was taken up in dry methylene chloride and boron tribromide(1 M in methylene chloride, 2.1 eq) was added at ambient temperature under nitrogen. After 6 hours, the reaction mixture was quenched with saturated sodium bicarbonate and extracted with methylene chloride. The organic layer was combined, dried over magnesium sulfate, and concentrated. Chromatography on silica gel afforded 4-(5-chloro-2-hydroxyphenyl)-3-(methylamino)-6-(trifluoromethyl)quinolin-2(1H)-one (1.03 g, 21%).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated
  4. customto isolated
  5. stirringthe reaction was stirred for 1 hour
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated
  9. waitAfter 6 hours
  10. customthe reaction mixture was quenched with saturated sodium bicarbonate
  11. extractionextracted with methylene chloride
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-228335c259044eeb992f2376983c47d0
Source dataset
uspto-grants-1999_10
Patent number
US05972961

Reaction notes

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