反应详情

温度

2.5 °C

A 3 L flask equipped with magnetic stirrer, ice bath and thermometer was charged with of 1 L of water containing 15.2 g of NaOH (5 eqv.) and the solution was cooled to 0-5° C. To this solution was added 50 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 75 g of NaCl and stirred. At the beginning everything was dissolved and a clear solution was formed. The mixture was stirred at it 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 32.7 g of pemetrexed disodium 2.5 hydrate in 83% yield as a white solid with a purity of 99.4% analyzed by HPLC.

1. customA 3 L 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 it 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