Sodium Hydroxide → D-Pemetrexed disodium

HRID 706415Notes

Reaction equation

HRID 706415 reaction equation
[CH:1]1[C:6]([CH2:7][CH2:8][C:9]2[C:13]3[C:14]([NH:16][C:17]([NH2:19])=[N:18][C:12]=3[NH:11][CH:10]=2)=[O:15])=[CH:5][CH:4]=[C:3]([C:20]([NH:22][C@@H:23]([C:29]([OH:31])=[O:30])[CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:21])[CH:2]=1.[OH-].[Na+:33]>CCO>[CH:5]1[C:6]([CH2:7][CH2:8][C:9]2[C:13]3[C:14]([NH:16][C:17]([NH2:19])=[N:18][C:12]=3[NH:11][CH:10]=2)=[O:15])=[CH:1][CH:2]=[C:3]([C:20]([NH:22][C@@H:23]([C:29]([O-:31])=[O:30])[CH2:24][CH2:25][C:26]([O-:28])=[O:27])=[O:21])[CH:4]=1.[Na+:33].[Na+:33]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 135565230Pemetrexed, (R)-

Product 1

HCID 135625269D-Pemetrexed disodium

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of Pemetrexed in EtOH containing 0% to 2% water (v/v) is heated to reflux and 1.85 eq of aq. NaOH (30% w/w) are added. The mixture is stirred at reflux until PXRD shows complete conversion. 0.15 eq of aq. NaOH (30% w/w) are added and stirring under reflux is continued for 2 h before the suspension is cooled to 20° C. to 30° C. Pemetrexed Disodium Form IV is isolated by filtration, washed with EtOH and dried in vacuo to constant weight.

Workup

  1. temperatureis heated
  2. temperatureto reflux
  3. temperatureat reflux until PXRD
  4. stirringstirring
  5. temperatureunder reflux
  6. temperatureis cooled to 20° C. to 30° C

Sources & evidence

ORD record
ord-106506ff70f0408097b32af7546e658d
Source dataset
uspto-grants-2015_11
Patent number
US09174991B2

Reaction notes

Loading…