Dimethylformamide → Sipoglitazar

HRID 350184

反応式

HRID 350184 の反応式
[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])=[CH:7][N:6]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[N:5]=1)[CH3:2].Cl[CH2:25][C:26]1[N:27]=[C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[S:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:1]([O:3][C:4]1[C:8]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:7][N:6]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([O:23][CH2:25][C:26]3[N:27]=[C:28]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[S:29][CH:30]=3)=[CH:21][CH:22]=2)[N:5]=1)[CH3:2]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2369694-(Chloromethyl)-2-phenyl-1,3-thiazoleHCID 23024904ethyl 3-[3-ethoxy-1-(4-hydroxybenzyl)-1H-pyrazol-4-yl]propionate

生成物 1

HCID 9825652Sipoglitazar収率 73.3%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

A mixture of ethyl 3-[3-ethoxy-1-(4-hydroxybenzyl)-1H-pyrazol-4-yl]propionate (1.50 g), 4-chloromethyl-2-phenylthiazole (1.05 g), potassium carbonate (1.30 g), and N,N-dimethylformamide (20 ml) was stirred at room temperature overnight. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then, with saturated aqueous sodium chloride solution, and dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and a colorless oily substance was obtained from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). A mixture of the obtained oily substance, 1 N aqueous sodium hydroxide solution (10 ml), tetrahydrofuran (10 ml), and ethanol (10 ml) was stirred at room temperature for two hours, diluted with 1 N hydrochloric acid (10 ml), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The obtained colorless crystals were collected by filtration and 3-[3-ethoxy-1-[4-(2-phenyl-4-thiazolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionic acid (1.60 g, yield: 73%) was obtained. This was recrystallized from acetone-hexane. Melting point: 114–115° C.

後処理

  1. extractionwas extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with water
  3. dry with materialwith saturated aqueous sodium chloride solution, and dried (MgSO4)
  4. concentrationconcentrated
  5. customa colorless oily substance was obtained from the fraction
  6. washeluted with ethyl acetate-hexane (1:2, volume ratio)
  7. additionA mixture of the obtained oily substance, 1 N aqueous sodium hydroxide solution (10 ml), tetrahydrofuran (10 ml), and ethanol (10 ml)
  8. stirringwas stirred at room temperature for two hours
  9. additiondiluted with 1 N hydrochloric acid (10 ml)
  10. extractionextracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. filtrationThe obtained colorless crystals were collected by filtration

出典と根拠

ORDレコード
ord-69b3de89a1404e36a03c849324b08a96
出典データセット
uspto-grants-2007_02
特許番号
US07179823B1

関連ノート

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