Triethylamine → Edaglitazone

HRID 854420Notes

Reaction equation

HRID 854420 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][O:15][C:16]1[C:24]2[CH:23]=[CH:22][S:21][C:20]=2[C:19]([CH:25]=[C:26]2[S:30][C:29](=[O:31])[NH:28][C:27]2=[O:32])=[CH:18][CH:17]=1.C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1.C(N(CC)CC)C>O>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][O:15][C:16]1[C:24]2[CH:23]=[CH:22][S:21][C:20]=2[C:19]([CH2:25][CH:26]2[S:30][C:29](=[O:31])[NH:28][C:27]2=[O:32])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)HCID 853192475-[[4-[2-(5-Methyl-2-phenyl-4-oxazolyl)ethoxy]-benzo[b]thien-7-yl]methylene]-2,4-thiazolidinedione

Product 1

HCID 9825701EdaglitazoneYield 80.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 35 ml stainless steel autoclave equipped with a magnetic stirring bar was charged under argon with 1.18 g (2.5 mmol) of 5-[[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-benzo[b]thien-7-yl]methylene]-2,4-thiazolidinedione, 0.985 g (3.75 mmol) of 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-diethyl ester, 3.56 g of Dowtherm A and 0.18 ml (1.25 mmol) of triethylamine. The autoclave was closed and immersed into an oil bath at 230° C. The reaction was run with stirring (800 rpm) for 20 min, then the autoclave was cooled in water to room temperature, opened and a sample was taken from the clear, yellowish solution for HPLC analysis (conversion was 99.8%). The reaction mixture was transferred into a 50 ml round flask and the autoclave was rinsed with a total of 16 ml of ethanol. Immediately after the ethanol was added, crystals started to form. The yellowish suspension was stirred for 1 h at room temperature and in an ice bath (ca. 2° C.) for 4 h. The precipitate was filtered with suction, the filter cake was washed with a total of 7 ml of ethanol and dried (60° C., 25 mbar, 17 h) to afford 0.94 g (77.3%) of 5-{[4-[2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy]benzo[b]thiophen-7-yl]methyl}-2,4-thiazolidinedione as a yellowish solid, which according to quantitative HPLC analysis (column: XTerra TM RP18, 3.5 mm, Waters Art. 186000442, mob. phase pH 4.5 buffer/acetonitrile with gradient, flow 1 ml/min, UV detection, retention time of starting material 16.3 min, retention time of product 12.5 min) was 95.5% pure.

Workup

  1. customThe autoclave was closed
  2. customimmersed into an oil bath at 230° C
  3. customThe reaction mixture was transferred into a 50 ml round flask
  4. washthe autoclave was rinsed with a total of 16 ml of ethanol
  5. additionImmediately after the ethanol was added
  6. customto form
  7. stirringThe yellowish suspension was stirred for 1 h at room temperature and in an ice bath (ca. 2° C.) for 4 h
  8. filtrationThe precipitate was filtered with suction
  9. washthe filter cake was washed with a total of 7 ml of ethanol
  10. customdried (60° C., 25 mbar, 17 h)

Sources & evidence

ORD record
ord-344b54829f854b7aba4366bb2008983a
Source dataset
uspto-grants-2007_08
Patent number
US07259176B2

Reaction notes

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