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

HRID 507667

반응식

HRID 507667 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매3회

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온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-45387975242b480cab24713f95061563
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786132B2

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