Hydrochloric Acid → 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

HRID 1193922

反応式

HRID 1193922 の反応式
[NH2:1]/[C:2](/[C:9]([F:12])([F:11])[F:10])=[CH:3]\[C:4]([O:6]CC)=O.[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]([N:26]2[C:4](=[O:6])[CH:3]=[C:2]([C:9]([F:10])([F:11])[F:12])[NH:1][C:27]2=[O:28])=[C:18]([F:29])[CH:17]=1

参加物

8

反応物 4

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

生成物 1

HCID 114285773-(4-chloro-2-fluoro-5-isopropoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1140Toluene溶媒2 回HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

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 recrystalized from diethyl ether/n-hexane. There is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, m.p. 195°-197° C.

後処理

  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 recrystalized from diethyl ether/n-hexane

出典と根拠

ORDレコード
ord-216d22aa144349878c456c1d375ec62f
出典データセット
uspto-grants-1989_03
特許番号
US04812164

関連ノート

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