Hydrochloric Acid → HCID 178508845, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence