Sodium hydride → 3-[3-(6-Methoxy-m-tolyl)-1,2-benzisothiazol-5-yl)-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione

HRID 1274547Notes

Reaction equation

HRID 1274547 reaction equation
[H-].[Na+].[NH2:3]/[C:4](/[C:11]([F:14])([F:13])[F:12])=[CH:5]\[C:6]([O:8]CC)=O.[CH3:15][O:16][C:17]1[C:22]([CH3:23])=[CH:21][C:20]([C:24]2[C:28]3[CH:29]=[C:30]([N:33]=[C:34]=[O:35])[CH:31]=[CH:32][C:27]=3[S:26][N:25]=2)=[CH:19][CH:18]=1>CCOCC.CN(C)C=O>[CH3:15][O:16][C:17]1[C:22]([CH3:23])=[CH:21][C:20]([C:24]2[C:28]3[CH:29]=[C:30]([N:33]4[C:6](=[O:8])[CH:5]=[C:4]([C:11]([F:12])([F:13])[F:14])[NH:3][C:34]4=[O:35])[CH:31]=[CH:32][C:27]=3[S:26][N:25]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 867560853-(6-Methoxy-m-tolyl)-1,2-benzisothiazol-5-yl isocyanate

Product 1

HCID 701000153-[3-(6-Methoxy-m-tolyl)-1,2-benzisothiazol-5-yl)-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedioneYield 70.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-10 °C

Procedure

A mixture of 60% sodium hydride in mineral oil (15.9 g, 0.397 mol) and N,N-dimethylformamide is cooled to -10° C., treated over one hour with a solution of ethyl 3-amino-4,4,4-trifluorocrotonate (72.7 g, 0.397 mol) in ether, warmed to and stirred at room temperature for 90 minutes, cooled to -70° C., treated over 80 minutes with a solution of 3-(6-methoxy-m-tolyl)-1,2-benzisothiazol-5-yl isocyanate (107 g, 0.361 mol) in N,N-dimethylformamide while maintaining the temperature below about -65° C., slowly warmed to and stirred at room temperature overnight, and poured onto ice. The resultant aqueous mixture is washed with ethyl acetate, acidified to pH 2 with concentrated hydrochloric acid, and extracted with diethyl ether. The organic extract is dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title product as an orange oil (110 g, 70.5%) which is identified by NMR spectral analyses.

Workup

  1. temperaturewarmed to and
  2. temperaturecooled to -70° C.
  3. temperaturewhile maintaining the temperature below about -65° C.
  4. temperatureslowly warmed to and
  5. stirringstirred at room temperature overnight
  6. additionpoured onto ice
  7. washThe resultant aqueous mixture is washed with ethyl acetate
  8. extractionextracted with diethyl ether
  9. extractionThe organic extract
  10. dry with materialis dried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0b44aaeb131f4aab9ec699def6de6d06
Source dataset
uspto-grants-2000_12
Patent number
US06156700

Reaction notes

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