Yield:-

Reaction Conditions:

with ammonia in ethyl acetate; pH=9.5 - 9.8 at -5 - 0;

Steps:

1.ii; 1.iv
To 4-necked flask (5 L) equipped with mechanical stirrer, thermometer pocket and gas sparger, was charged ethyl acetate (2.7 L) and crude 0,0-DMDTPA (270 grams) (obtained from Step (i)). Cooled the above reaction mass to -5 ⁰C and purged the ammonia gas in the reaction vessel at a temperature of -5 - 0 °C till pH was reached to 9.5 - 9.8. After the desired pH was achieved, reaction mass was maintained at -5 to 0°C for a period of 2 hours. The reaction mass was then filtered and washed with ethyl acetate (270 mL). Suck dried and unloaded. The wet weight of obtained ammonium salt was 240 - 255 grams. Dried at 25 - 28 °C under vacuum for the period of 5 hours or till constant weight was achieved.The dry weight of ammonium salt was 233 - 240 grams. HPLC purity: 99.33 %.; Step (iv): Preparation of 2^nd ammonium salt of O,O-DMDTPA To 4-necked flask (3 L) equipped with mechanical stirrer, thermometer pocket and gas sparge, was charged ethyl acetate (1.84 L) and regenerated O, O-DMDTPA (184 grams) (obtained from step (Hi)). Cooled the above reaction mass to -5 °C and purged the ammonia gas in the reaction vessel at a temperature of -5 to 0 °C till pH of 9.5 - 9.8 was reached. After the desired pH was achieved, reaction mass was maintained at -5 to 0 ⁰C for the period of 2 hours. The above reaction mass was then filtered and washed with ethyl acetate (184 mL). Suck dried and unloaded. The wet weight of obtained ammonium salt was 172 - 175 grams. Dried at 25 - 28 °C under vacμum for the period of 5 hours or till constant weight was achieved. The dry weight of ammonium salt was 162 - 166 grams. HPLC purity: 99.68%

References:

SUVEN LIFE SCIENCES LIMITED WO2009/7998, 2009, A1 Location in patent:Page/Page column 8; 9