Ethanol → Trimetrexate Ascorbate

HRID 1384091Notes

Reaction equation

HRID 1384091 reaction equation
[O:1]=[C:2]1[O:8][C@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[C:5]([OH:6])=[C:3]1[OH:4].C(N(CCCC)CCCC)CCC.C(O)C.[CH3:29][C:30]1[C:35]2[C:36]([NH2:41])=[N:37][C:38]([NH2:40])=[N:39][C:34]=2[CH:33]=[CH:32][C:31]=1[CH2:42][NH:43][C:44]1[CH:49]=[C:48]([O:50][CH3:51])[C:47]([O:52][CH3:53])=[C:46]([O:54][CH3:55])[CH:45]=1.FC(F)(F)C([O-])=O>CC(O)C>[CH3:29][C:30]1[C:35]2[C:36]([NH2:41])=[N:37][C:38]([NH2:40])=[N:39][C:34]=2[CH:33]=[CH:32][C:31]=1[CH2:42][NH:43][C:44]1[CH:49]=[C:48]([O:50][CH3:51])[C:47]([O:52][CH3:53])=[C:46]([O:54][CH3:55])[CH:45]=1.[O:1]=[C:2]1[O:8][C@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[C:5]([O-:6])=[C:3]1[OH:4]

Participants

6

Reactant 4

HCID 702EthanolHCID 7622TributylamineHCID 54670067L-Ascorbic AcidHCID 131722762HCID 131722762, compound

Product 1

HCID 178493113Trimetrexate AscorbateYield 59.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

This part of the preparation was carried out, as far as possible, under a nitrogen atmosphere. Equivalent quantities of ascorbic acid (0.463 g) and tributylamine (0.487 g) were heated in 20 ml of 200 proof ethanol at 60° C. to give a clear solution. This was cooled to room temperature and a half-equivalent of trimetrexate trifluoroacetate (0.635 g; assumed unsolvated) added and the mixture heated to near reflux to give a clear yellow solution. To the hot solution was added 50 ml of 2-propanol. A light-colored flocculent solid was immediately precipitated. The mixture was heated at 50° C. for 3 minutes, and then allowed to stand in air for about 1.5 hours. The solid was collected, washed with 2:1 2-propanol/ethanol at room temperature, and immediately transferred to a desiccator and dried (diaphragm pump vacuum) over P2O5 to give 0.425 g of the salt as a very pale yellow-green powder.

Workup

  1. customto give a clear solution
  2. temperaturethe mixture heated
  3. temperatureto near reflux
  4. customto give a clear yellow solution
  5. customA light-colored flocculent solid was immediately precipitated
  6. temperatureThe mixture was heated at 50° C. for 3 minutes
  7. customThe solid was collected
  8. washwashed with 2:1 2-propanol/ethanol at room temperature
  9. customimmediately transferred to a desiccator
  10. dry with materialdried (diaphragm pump vacuum) over P2O5

Sources & evidence

ORD record
ord-08e7a5ef0960439182785a734a63ce72
Source dataset
uspto-grants-2001_07
Patent number
US06258821B1

Reaction notes

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