Indomethacin → 1-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid-3-pyridylmethyl ester

HRID 261450

反応式

HRID 261450 の反応式
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][C:20]([OH:22])=[O:21])=[C:9]2[CH3:23])=[O:7])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32]([CH2:36]O)[CH:31]=1.C(N(CC)CC)C>C1C=CC=CC=1.O1CCCC1.O>[N:30]1[CH:35]=[CH:34][CH:33]=[C:32]([CH2:36][O:21][C:20](=[O:22])[CH2:19][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=3)[N:8]([C:6](=[O:7])[C:5]3[CH:24]=[CH:25][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:9]=2[CH3:23])[CH:31]=1

参加物

8

反応物 4

HCID 3715IndomethacinHCID 75103-PyridinemethanolHCID 8471TriethylamineHCID 24386Thionyl Chloride

生成物 1

HCID 203950501-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid-3-pyridylmethyl ester収率 79.7%

試薬・触媒・溶媒 3

HCID 241Benzene溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A mixture of 3.0 g of 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid and 3.0 g of thionyl chloride was refluxed in 70 ml of benzene for 3 hours. After cooling, the solvent was distilled off under reduced pressure to leave a residue. The residue was dissolved in 20 ml of tetrahydrofuran. This solution was added to a solution of 1.0 g of 3-pyridylmethanol in 70 ml of tetrahydrofuran under cooling. To this mixture was carefully added 0.95 g of triethylamine and stirring was continued for 2 hours at room temperature. After the reaction was complete, the solvent was removed by distillation under reduced pressure to leave a residue. After addition of water to the residue, an oily substance was obtained and extracted with chloroform. The extract was applied on a column of silica gel and the adsorbate was eluted with ether to give crystals. Recrystallization of the crystals from a mixed solvent of ethyl acetate ester and ether yielded 3.0 g of 1-(p-chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid-3 -pyridylmethyl ester, melting at 116°-118° C. Analysis--Calculated for C25H21ClN2O4 : C, 66.89; H, 4.72; N, 6.24. Found: C, 67.06; H, 4.68; N, 6.11.

後処理

  1. temperatureAfter cooling
  2. distillationthe solvent was distilled off under reduced pressure
  3. customto leave a residue
  4. temperatureunder cooling
  5. customthe solvent was removed by distillation under reduced pressure
  6. customto leave a residue
  7. customan oily substance was obtained
  8. extractionextracted with chloroform
  9. washthe adsorbate was eluted with ether
  10. customto give crystals
  11. customRecrystallization of the crystals from a mixed solvent of ethyl acetate ester and ether

出典と根拠

ORDレコード
ord-56bb7ac1f25a47bc819591a99a670915
出典データセット
uspto-grants-1979_08
特許番号
US04165428

関連ノート

読み込み中…