ChemicalBook CAS DataBase List Pioglitazone

Pioglitazone synthesis

9synthesis methods

Product Name:Pioglitazone
CAS Number:105355-27-9
Molecular formula:C19H20N2O3S
Molecular Weight:356.44

5-[4-[2-(5-Ethyl-2-Pyridyl)Ethoxy]-2-Imino-4-Thiazoldione

136401-69-9
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105355-27-9
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Yield:105355-27-9 99%

Reaction Conditions:

Stage #1: 5-{4-[2-(5-ethyl-pyridin-2-yl)ethoxy]benzylidene}-2,4-thiazolidinedionewith sodium hydroxide in tetrahydrofuran;water at 20; for 0.166667 h;
Stage #2: with sodium tetrahydroborate;butane-2,3-dione dioxime;cobalt(II) chloride in tetrahydrofuran;DMF (N,N-dimethyl-formamide);water at 15; for 6 h;

Steps:

4 [EXAMPLE 4;] Production of [5-F 4-[2-(5-ETHYL-2-PYRIDYL)] ethoxy] [BENZYL}-274-THIAZOLIDINEDIONE]

A 2 L three-necked flask equipped with a mechanical stirrer and thermometer is charged with 53.16 g (150 mmol) of [5-{4-[2-(5-ETHYL-2-PYRIDYL) ETHOXY] BENZYLIDENE}-2,] 4 thiazolidinedione, 750 ml of water, 180 ml of tetrahydrofuran, and 60 ml of [L.] ON sodium hydroxide. The mixture is stirred at room temperature for 10 minutes and cooled to [15 °C.] To the cooled mixture is added slowly 15 ml of catalyst solution, prepared by dissolving 0.696 g (6 mmol) [OF DIMETHYLGLYOXIME] and 0. [036] g (0.15 mmol) of cobaltous chloride hexahydrate in 15 ml [OF DIMETHYLFORMAMIDE. A SOLUTION OF] 11.34 g (300 mmol) of sodium borohydride in 15 ml of [L.] ON sodium hydroxide diluted with 70 ml of water is added dropwise to the resulting mixture at [15 °C] over 3 hours. The reaction mixture is stirred at 15 [°C] for 3 hours. The reaction mixture is quenched by dropwise addition of 78 ml of acetone to destroy any remaining of sodium borohydride. The resulting solution is acidified by the dropwise addition of 24 [ML] of glacial acetic acid diluted with 52 ml of water at room temperature (22- [24 °C)] until the pH of the solution becomes 6.0-6. 5. Upon acidification, the product precipitates as off white solids. The slurry is cooled to 0-5 [°C] in an ice bath and stirred for 30 minutes prior to filtration. The collected product is washed with three 450 ml portions of water and dried at [55 °C] in the vacuum oven for [18] hours to give 53 g of product as off- white solid (yield 99%).

References:

WO2004/810,2003,A1 Location in patent:Page 8

144809-28-9 Synthesis