Acetic Acid → 5-Bromo-2-chloro-4-(thiophen-2-yl)pyrimidine

HRID 507667

反応式

HRID 507667 の反応式
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[Li].[Br:7][C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[N:12][CH:13]=1.C(O)(=O)C.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1COCC1.CO>[Br:7][C:8]1[C:9]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[N:10][C:11]([Cl:14])=[N:12][CH:13]=1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 6066655-Bromo-2-chloropyrimidineHCID 178418439HCID 178418439、化合物

生成物 1

HCID 574288715-Bromo-2-chloro-4-(thiophen-2-yl)pyrimidine

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-78 °C

実験手順

Thienyl lithium (1.0 M in THF, 26 mL, 26 mmol) was diluted with anhydrous THF (65 mL) and the mixture cooled down to −78° C. under a nitrogen atmosphere. 5-Bromo-2-chloropyrimidine, dissolved in 10 mL of tetrahydofuran, was added to the reaction mixture dropwise. The reaction was allowed to stir for 1 h and then warmed to −20° C. Acetic acid (1.5 mL) and methanol (1.2 mL) were successively added to the reaction mixture. The reaction was stirred for 15 min and a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (5.9 g, 20 mmol) in 10 mL of THF was added. The reaction was stirred for an additional 15 min and then the cooling bath was removed. The mixture was stirred for 1 h and then cooled to 0° C. with an ice bath. 5 N sodium hydroxide (5.2 mL) was added to the reaction mixture and stirred for 5 min. The reaction was then diluted with ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, concentrated and purified by flash chromatography on silica gel using 5% ethyl acetate in hexanes as an eluent to obtain a yellow solid. Yield=3.6 g. MS (M+H)+ 275/277.

後処理

  1. additionwas added to the reaction mixture dropwise
  2. temperaturewarmed to −20° C
  3. stirringThe reaction was stirred for 15 min
  4. stirringThe reaction was stirred for an additional 15 min
  5. customthe cooling bath was removed
  6. stirringThe mixture was stirred for 1 h
  7. temperaturecooled to 0° C. with an ice bath
  8. addition5 N sodium hydroxide (5.2 mL) was added to the reaction mixture
  9. stirringstirred for 5 min
  10. additionThe reaction was then diluted with ethyl acetate (50 mL) and water (50 mL)
  11. washThe organic layer was washed with saturated aqueous sodium bicarbonate, water and brine
  12. dry with materialThe organic layer was then dried with sodium sulfate
  13. concentrationconcentrated
  14. custompurified by flash chromatography on silica gel using 5% ethyl acetate in hexanes as an eluent
  15. customto obtain a yellow solid

出典と根拠

ORDレコード
ord-45387975242b480cab24713f95061563
出典データセット
uspto-grants-2010_08
特許番号
US07786132B2

関連ノート

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