Acetic Acid → 4-(6-Bromobenzo[b]thiophen-2-yl)-2-chloro-5-methylpyrimidine

HRID 1986252

反応式

HRID 1986252 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[CH:8][S:7][C:6]=2[CH:10]=1.C([N-]C(C)C)(C)C.[Li+].[Cl:19][C:20]1[N:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=1.C(O)(=O)C.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C1COCC1.CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([C:22]3[C:23]([CH3:26])=[CH:24][N:25]=[C:20]([Cl:19])[N:21]=3)[S:7][C:6]=2[CH:10]=1

参加物

8

反応物 5

HCID 176Acetic AcidHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 5817192-Chloro-5-methylpyrimidineHCID 2724682Lithium diisopropylamideHCID 127444006-Bromo-benzo[b]thiophene

生成物 1

HCID 866253744-(6-Bromobenzo[b]thiophen-2-yl)-2-chloro-5-methylpyrimidine収率 39%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 22742125Tetrahydrofuran heptane ethylbenzol溶媒

反応条件

温度
-75 °C

実験手順

A solution of 6-bromobenzo[b]thiophene (5.00 g, 23.5 mmol) in THF (50 mL) is cooled to −70° C. Lithium diisopropylamide (12.9 mL of a 2 M solution in heptane/THF/ethylbenzene, 25.8 mmol) is added dropwise over 5 minutes. After stirring for 40 minutes at −75° C., the mixture is removed from the cold bath and allowed to warm to 0° C. over 15 minutes and then recooled to −35° C. 2-Chloro-5-methylpyrimidine (3.02 g, 23.5 mmol) is added to the mixture as a solid in one portion and the resultant mixture is allowed to stir for 30 minutes at −35° C. Acetic acid (1.55 g, 25.8 mmol) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (5.60 g, 24.7 mmol) are added in one portion to the mixture before it is allowed to stir at room temperature for 16 hours. Then the mixture is concentrated under reduced pressure, suspended in warm dichloromethane, eluted through a pad of silica in dichloromethane (1 L) and concentrated under reduced pressure. The crude material is subjected to chromatography on silica gel, eluting with dichloromethane in hexanes 50-100%. The resulting material is sonicated in ether (100 mL) and filtered to provide the title compound as an orange solid (3.08 g, 39% yield).

後処理

  1. customthe mixture is removed from the cold bath
  2. temperatureto warm to 0° C. over 15 minutes
  3. customrecooled to −35° C
  4. stirringto stir for 30 minutes at −35° C
  5. stirringto stir at room temperature for 16 hours
  6. concentrationThen the mixture is concentrated under reduced pressure
  7. washeluted through a pad of silica in dichloromethane (1 L)
  8. concentrationconcentrated under reduced pressure
  9. washeluting with dichloromethane in hexanes 50-100%
  10. customThe resulting material is sonicated in ether (100 mL)
  11. filtrationfiltered

出典と根拠

ORDレコード
ord-58ec3b70e0814499bda04eda6cb201c5
出典データセット
uspto-grants-2009_06
特許番号
US07547691B2

関連ノート

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