反应详情

温度

2.5 °C

A 500 mL flask equipped with magnetic stirrer, ice bath and thermometer was charged with 95 mL of water containing 1.52 g of NaOH (5 eqv.) and the solution was cooled to 0-5° C. To this solution was added 5 g of N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid diethylester p-toluenesulfonic acid salt. The mixture was stirred at 0-5° C. for 30-35 minutes. The pH was adjusted to 7-9 by adding 1N HCl. The mixture was warmed to rt. To the solution was added 10 gr of NaCl and stirred. At the beginning everything was dissolved and a clear solution was formed. The mixture was stirred at rt for 50-60 minutes and pemetrexed disodium was precipitated. The solid was isolated by filtration and washed with 10 ml of ethanol/water (7/2 v/v). The solid was dried in a vacuum oven at 50-55° C. for 5-6 hours to give 3.19 g of pemetrexed disodium 2.5 hydrate in 81% yield as a white solid with a purity of 99.5% analyzed by HPLC.

1. customA 500 mL flask equipped with magnetic stirrer, ice bath
2. temperatureThe mixture was warmed to rt
3. stirringstirred
4. dissolutionAt the beginning everything was dissolved
5. customa clear solution was formed
6. stirringThe mixture was stirred at rt for 50-60 minutes
7. custompemetrexed disodium was precipitated
8. customThe solid was isolated by filtration
9. washwashed with 10 ml of ethanol/water (7/2 v/v)
10. customThe solid was dried in a vacuum oven at 50-55° C. for 5-6 hours