Sodium Hydroxide → HCID 58485566、化合物

HRID 1012727

反応式

HRID 1012727 の反応式
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1.[N:15]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[C@@H:17]([NH:23][C:24]([C:26]1[O:27][C:28]3[C:34](Br)=[CH:33][C:32]([F:36])=[CH:31][C:29]=3[CH:30]=1)=[O:25])[CH2:16]2.[OH-].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[N:15]12[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22]1)[C@@H:17]([NH:23][C:24]([C:26]1[O:27][C:28]3[C:34]([C:7]4[CH:8]=[CH:9][C:4]([O:3][C:2]([F:14])([F:13])[F:1])=[CH:5][CH:6]=4)=[CH:33][C:32]([F:36])=[CH:31][C:29]=3[CH:30]=1)=[O:25])[CH2:16]2

参加物

6

反応物 3

HCID 14798Sodium HydroxideHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 59341405N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-fluoro-7-bromo-1-benzofuran-2-carboxamide

生成物 1

HCID 58485566HCID 58485566、化合物

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

A mixture of 40 mg (0.29 mmol) of 4-(trifluoromethoxy)phenylboronic acid, 70 mg (0.19 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-fluoro-7-bromo-1-benzofuran-2-carboxamide (Example 5A), 0.57 ml (0.57 mmol) of 1N sodium hydroxide solution, 14 mg (0.02 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride and 2 ml of DMF is heated at 85° C. overnight. The solvent is removed under reduced pressure. The crude product is mixed with 1N sodium hydroxide solution and extracted three times with a total of 100 ml of ethyl acetate. The combined organic phases are dried over magnesium sulphate, and the solvent is removed under reduced pressure. The crude product is taken up in methanol and shaken together with acidic ion exchanger (Dowex® WX2-200) for about 20 min. The loaded ion exchanger is washed three times with 30 ml of methanol each time, then with water, again with methanol, with dichloromethane, again with methanol, with THF and finally once more with methanol. The product is eluted with methanol/triethylamine 95:5. The solvent is removed in a rotary evaporator under reduced pressure. Silica gel 60 (Merck, Darmstadt; eluent: dichloromethane/triethylamine 100:1, then dichloromethane/methanol/triethylamine 100:1:1 to dichloromethane/methanol/triethylamine 100:10:1) is used for final purification. The solvent is removed under reduced pressure. Finally, the last residues of solvent are removed under high vacuum. 52 mg (61% of theory) of the title compound are isolated.

後処理

  1. customThe solvent is removed under reduced pressure
  2. additionThe crude product is mixed with 1N sodium hydroxide solution
  3. extractionextracted three times with a total of 100 ml of ethyl acetate
  4. dry with materialThe combined organic phases are dried over magnesium sulphate
  5. customthe solvent is removed under reduced pressure
  6. washThe loaded ion exchanger is washed three times with 30 ml of methanol each time
  7. washThe product is eluted with methanol/triethylamine 95:5
  8. customThe solvent is removed in a rotary evaporator under reduced pressure
  9. custompurification
  10. customThe solvent is removed under reduced pressure
  11. customFinally, the last residues of solvent are removed under high vacuum

出典と根拠

ORDレコード
ord-c982d19211ef419db233d7cee128153a
出典データセット
uspto-grants-2011_07
特許番号
US07977485B2

関連ノート

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