Hydrochloric Acid → HCID 70395308, compound

HRID 1722931Notes

Reaction equation

HRID 1722931 reaction equation
[NH2:1]/[C:2](/[C:9]([F:12])([F:11])[F:10])=[CH:3]\[C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].[Cl:15][C:16]1[C:21]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:20][C:19]([N:26]=[C:27]=[O:28])=[C:18]([F:29])[CH:17]=1.Cl>C1(C)C=CC=CC=1.CN(C)C=O.O>[Cl:15][C:16]1[C:21]([O:22][CH:23]([CH3:24])[CH3:25])=[CH:20][C:19]([NH:26][C:27](=[O:28])[NH:1]/[C:2](/[C:9]([F:10])([F:11])[F:12])=[CH:3]\[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[C:18]([F:29])[CH:17]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 132729244-Chloro-2-fluoro-5-isopropoxyphenyl isocyanate

Product 1

HCID 70395308HCID 70395308, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1.0 g of ethyl 3-amino-4,4,4-trifluorocrotonate in 10 ml of absolute toluene is added dropwise while stirring at 0° C. during 15 minutes to a suspension of 0.24 g of a 55% sodium hydride dispersion in 20 ml of absolute dimethylformamide and the mixture is stirred at 0° C. for 15 minutes. The reaction mixture is subsequently cooled to -30° C. and treated with a solution of 1.26 g of 4-chloro-2-fluoro-5-isopropoxyphenyl isocyanate in 10 ml of absolute toluene. The temperature rises rapidly to -10° C. and the reaction mixture is thereafter stirred at room temperature for 2 hours. The reaction mixture is poured into a solution of 3 ml of 2N hydrochloric acid and 500 ml of water and the aqueous mixture is extracted twice with 100 ml of ethyl acetate each time, and the organic phases are washed twice with 50 ml of water each time, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether/n-hexane. Via ethyl 3-[3-(4-chloro-2-fluoro-5 -isopropoxyphenyl)ureido]-4,4,4-trifluorocrotonate (m.p. 144°-146° C.), which is not isolated, there is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-6 -trifluoromethyl-2,4(1H,3H)-pyrimidinedione, m.p. 195°-197° C.

Workup

  1. temperatureThe reaction mixture is subsequently cooled to -30° C.
  2. customrises rapidly to -10° C.
  3. stirringthe reaction mixture is thereafter stirred at room temperature for 2 hours
  4. extractionthe aqueous mixture is extracted twice with 100 ml of ethyl acetate each time
  5. washthe organic phases are washed twice with 50 ml of water each time
  6. dry with materialdried over anhydrous sodium sulphate
  7. customevaporated to dryness under reduced pressure
  8. customThe residue is recrystallized from diethyl ether/n-hexane

Sources & evidence

ORD record
ord-93b43e1908d741999601e76a2bb3bb0f
Source dataset
uspto-grants-1989_08
Patent number
US04859229

Reaction notes

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