Dimethylformamide → Sipoglitazar

HRID 350184Notes

Reaction equation

HRID 350184 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

HCID 9825652SipoglitazarYield 73.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-69b3de89a1404e36a03c849324b08a96
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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