Sodium Carbonate → 3-(4-chloro-2-fluoro-5-hydroxyphenyl)6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

HRID 1722979Notes

Reaction equation

HRID 1722979 reaction equation
[NH2:1]/[C:2](/[C:9]([F:12])([F:11])[F:10])=[CH:3]\[C:4]([O:6]CC)=O.[H-].[Na+].C(=O)(OC)[O:16][C:17]1[CH:22]=[C:21]([N:23]=[C:24]=[O:25])[C:20]([F:26])=[CH:19][C:18]=1[Cl:27].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C)C=O.O>[Cl:27][C:18]1[C:17]([OH:16])=[CH:22][C:21]([N:23]2[C:4](=[O:6])[CH:3]=[C:2]([C:9]([F:10])([F:11])[F:12])[NH:1][C:24]2=[O:25])=[C:20]([F:26])[CH:19]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 143708702-Chloro-4-fluoro-5-isocyanatophenyl methyl carbonate

Product 1

HCID 177702713-(4-chloro-2-fluoro-5-hydroxyphenyl)6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4.67 g of ethyl 3-amino-4,4,4-trifluorocrotonate in 15 ml of toluene is added dropwise while stirring at 0° C. during 20 minutes to a suspension of 1.11 g of a 55% sodium hydride dispersion in 30 ml of absolute dimethylformamide, and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is subsequently cooled to -40° C. and a solution of 6.24 g of 2-chloro-4-fluoro-5-isocyanatophenyl methyl carbonate in 30 ml of toluene is added dropwise during 5 minutes. The reaction mixture is stirred at room temperature for 1 hour and stirred for a further 30 minutes with a solution of 5.40 g of sodium carbonate in 100 ml of water. The aqueous phase is separated. extracted twice with 50 ml of diethyl ether each time and adjusted to pH 1 with 8 ml of 2N hydrochloric acid. The mixture is extracted twice with 100 ml of diethyl ether each time and the organic phases are washed with water. dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether/n-hexane. There is obtained 3-(4-chloro-2-fluoro-5-hydroxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, m.p. 223°-225° C.

Workup

  1. temperatureThe reaction mixture is subsequently cooled to -40° C.
  2. stirringThe reaction mixture is stirred at room temperature for 1 hour
  3. customThe aqueous phase is separated
  4. extractionextracted twice with 50 ml of diethyl ether each time
  5. extractionThe mixture is extracted twice with 100 ml of diethyl ether each time
  6. washthe organic phases are washed with water
  7. dry with materialdried over anhydrous sodium sulphate
  8. customevaporated to dryness under reduced pressure
  9. customThe residue is recrystallized from diethyl ether/n-hexane

Sources & evidence

ORD record
ord-28ed8116c55c456e93e7da006cefc6a6
Source dataset
uspto-grants-1989_08
Patent number
US04859229

Reaction notes

Loading…