Ethanol → 3-(4-Pyridinylamino)-1h-indole-2-carboxylic acid potassium salt

HRID 1376116ノート

反応式

HRID 1376116 の反応式
C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1[NH2:15])=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])C.C(O)C.[OH-].[K+:20].[K+].NC1[C:31]2[C:26](=C[CH:28]=[CH:29][CH:30]=2)[NH:25]C=1C([O-])=O>O.C(#N)C>[K+:20].[N:25]1[CH:26]=[CH:31][C:30]([NH:15][C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:4]([O-:3])=[O:5])=[CH:29][CH:28]=1

参加物

7

反応物 4

HCID 702EthanolHCID 14797Potassium HydroxideHCID 732887Ethyl 3-amino-1H-indole-2-carboxylate2 回HCID 236745823-Amino-1h-indole-2-carboxylic acid potassium salt

生成物 1

HCID 690066653-(4-Pyridinylamino)-1h-indole-2-carboxylic acid potassium salt収率 140%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
75 °C

実験手順

Charge a mixture of 7.50 kg (26.66 mol) of 3-amino-1H-indole-2-carboxylic acid ethyl ester, 37.5L of ethanol and 37.5 L of 4M KOH to a 30-gal reactor and heat to 75° C. over 30 min. Monitor the progress of the reaction by HPLC (Column—150×3.9 mm Waters Symmetry C18, 5 micron; mobile phase—20% acetonitrile/80% 0.1% TFA in water; flow rate—1.0 mL/min; wavelength—225 nm; RT: 3-amino-1H-indole-2-carboxylic acid potassium salt—3.3 min; 3-amino-1H-indole-2-carboxylic acid ethyl ester—6.0 min). Typically achieve, a 100% conversion within 3 h. Cool the mixture to 25° C. over 2 h and concentrate at 50–60° C./50 torr to a residue. Add a total of 37.5 L of water and heat the mixture to and hold at 85° C. for 30 min. Cool the mixture to 10° C. over 2 hours, and then further cool to and hold at 5° C. for 2 hours. Filter off the solid that forms, wash with a total of 10 L of 4M KOH solution and air dry. Further dry the solid at 35° C. in a forced air oven for 72 h to give 10.9 kg, 140% yield of the title compound: HPLC analysis 70.7% pure.

後処理

  1. additionCharge
  2. temperatureCool the mixture to 25° C. over 2 h
  3. concentrationconcentrate at 50–60° C./50 torr to a residue
  4. additionAdd a total of 37.5 L of water
  5. temperatureheat the mixture to and
  6. waithold at 85° C. for 30 min
  7. temperatureCool the mixture to 10° C. over 2 hours
  8. temperaturefurther cool to and
  9. waithold at 5° C. for 2 hours
  10. filtrationFilter off the solid that forms
  11. washwash with a total of 10 L of 4M KOH solution and air
  12. customdry
  13. customFurther dry the solid at 35° C. in a forced air oven for 72 h

出典と根拠

ORDレコード
ord-e9072bbacf5049c99e6d8034ddef78be
出典データセット
uspto-grants-2007_01
特許番号
US07169925B2

反応ノート

読み込み中…