Sodium Hydroxide → D-Pemetrexed disodium

HRID 706412Notes

Reaction equation

HRID 706412 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.[Na].[OH-].[Na+:34]>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+:34].[Na+:34]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 136413199Pemetrexed Monosodium

Product 1

HCID 135625269D-Pemetrexed disodium

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of Pemetrexed Monosodium in EtOH containing 0-2% water (v/v) was heated to reflux and 0.85 eq of aq. NaOH (30% w/w) were added. The mixture was stirred at reflux until PXRD showed complete conversion. 0.15 eq of aq. NaOH (30% w/w) were added and stirring under reflux was continued for 2 h before the suspension was cooled to 20° C. to 30° C. Pemetrexed Disodium Form IV was isolated by filtration, washed with EtOH and dried in vacuo at 50° C. at 5 mbar to constant weight.

Workup

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

Sources & evidence

ORD record
ord-0bda0ddec033430da9a7d29d790aca28
Source dataset
uspto-grants-2015_11
Patent number
US09174991B2

Reaction notes

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