Phosgene → Pirogliride Tartrate

HRID 2057628Notes

Reaction equation

HRID 2057628 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C:3]1=O.C(Cl)(Cl)=O.[C:12]1([NH:18][C:19]([N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[NH:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.[OH-].[Na+].[C:35]([OH:44])(=[O:43])[C@@H:36]([C@H:38]([C:40]([OH:42])=[O:41])[OH:39])[OH:37]>C1(C)C=CC=CC=1.C(Cl)Cl.C(O)(C)C>[C:40]([C@@H:38]([C@H:36]([C:35]([OH:44])=[O:43])[OH:37])[OH:39])([OH:42])=[O:41].[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C:3]1=[N:20][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)=[N:18][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

10

Reactant 6

HCID 6371PhosgeneHCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidoneHCID 14798Sodium HydroxideHCID 444305L-Tartaric acidHCID 178511988HCID 178511988, compound

Product 1

HCID 44103Pirogliride Tartrate

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a cooled solution of 1.98 g (0.02 mole) of 1-methyl-2-pyrrolidone in dry toluene is added 3.95 g (0.04 mole) of phosgene. The resulting mixture is allowed to stir under N2 to room temperature over 45 minutes to give white crystals. The excess COCl2 and solvent are removed with the aid of a filter stick (under N2). Fresh toluene is added, then removed under vacuum in order to remove residual phosgene. The crystals are washed in this way with fresh toluene two more times and then dissolved in dry CH2Cl2 followed by the addition of 1.89 g (0.01 mole) of N-phenyl-1-pyrrolidinecarboximidamide and 1.01 g (0.01 mole) of triethylamine. The resulting mixture is stirred overnight under N2. The mixture is taken to dryness in vacuo, the residue dissolved in CH2Cl2 and the latter solution treated with NaOH (50%) in ice. The organic layer, which contains the free base form of the product, is separated, dried over anhydrous K 2 CO3, filtered and taken to dryness in vacuo affording an oily residue. The oil is dissolved in isopropanol followed by addition of L-(+)-tartaric acid to about pH 6-7. The resulting crystals are recrystallized from isopropanol to give pure product, N-(1-methyl-2-pyrrolidinylidene)-N'-phenyl-1-pyrrolidinecarboximidamide L-(+)-tartrate, m.p. 155°-156° C.

Workup

  1. customto give white crystals
  2. customThe excess COCl2 and solvent are removed with the aid of a filter stick (under N2)
  3. additionFresh toluene is added
  4. customremoved under vacuum in order
  5. customto remove residual phosgene
  6. washThe crystals are washed in this way with fresh toluene two more times
  7. dissolutiondissolved in dry CH2Cl2
  8. stirringThe resulting mixture is stirred overnight under N2
  9. customis separated
  10. customdried over anhydrous K 2 CO3
  11. filtrationfiltered
  12. customaffording an oily residue
  13. customThe resulting crystals are recrystallized from isopropanol

Sources & evidence

ORD record
ord-6ae38d15434e4a5d87bc342d0ef6572b
Source dataset
uspto-grants-1980_07
Patent number
US04211867

Reaction notes

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