A process of making a pemetrexed salt comprising: a) reacting a compound of formula II or an acid salt thereof, wherein each of R1 and R2 is independently a C1-C6 alkyl group, with an aqueous basic solution at a temperature of no more than 10° C. to obtain a first mixture comprising the pemetrexed salt; b) isolating the pemetrexed salt from the first mixture.