3,5-diiodo-4-hydroxyphenylpropionic acid synthesis

Yield:13811-11-5 93%

Reaction Conditions:

Stage #1: 4-hydroxyphenylpropionic acidwith pyridine;dihydrogen peroxide;iodine in water at 40; for 2 h;
Stage #2: with hydrogenchloride in water at 20;Product distribution / selectivity;

Steps:

1

A mixture of 1.66 g (10 mmol) of 3-(4-hydroxyphenyl)propionic acid, 3 g (38 mmol) of pyridine and 2.54 g (10 mmol) of molecular iodine was maintained at 40°C, and 2.5 g (22 mmol as hydrogen peroxide) of a 30% aqueous hydrogen peroxide was dropped thereto over 0.4 hour. After the completion of addition of the aqueous hydrogen peroxide, the reaction solution was maintained at 40°C, and stirred for 1.6 hour. Then, 5 g of a 20% aqueous sodium sulfite solution was added thereto. At room temperature, the reaction solution was added little by little to 20 g of a 2N aqueous hydrochloric acid solution under stirring. After the whole amount of the reaction solution was added thereto, 60 g of water was added thereto. The precipitated crystals were separated by filtration and vacuum dried at 70°C to obtain 3.9 g of crystals. According to analyses of the crystals and the mother liquid with high performance liquid chromatography, conversion of 3-(4-hydroxyphenyl)propionic acid was 100%, selectivity of 3-(4-hydroxy-3,5diiodophenyl)propionic acid was 94% on both substrate basis and iodine basis, selectivity of 3-(4-hydroxy-3iodophenyl)propionic acid was 0.4%, isolated yield of 3-(4-hydroxy-3,5diiodophenyl)propionic acid was 93%, and crystal purity of 3-(4-hydroxy-3,5diiodophenyl)propionic acid was 99%.

References:

EP2199271,2010,A1 Location in patent:Page/Page column 5