Oxalic Acid → HCID 20065665, compound

HRID 359117Notes

Reaction equation

HRID 359117 reaction equation
[CH3:1][N:2]([CH3:13])[CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[NH:4]1.[H-].[Na+].[C:16]1([C:22]2[CH2:23][CH2:24][N:25]([CH2:28][CH2:29][CH2:30]Br)[CH2:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[C:32]([OH:37])(=[O:36])[C:33]([OH:35])=[O:34]>CN(C)C=O.C(Cl)Cl.C(C(C)=O)C>[C:32]([OH:37])(=[O:36])[C:33]([OH:35])=[O:34].[CH3:1][N:2]([CH3:13])[CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[N:4]1[CH2:30][CH2:29][CH2:28][N:25]1[CH2:24][CH:23]=[C:22]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:27][CH2:26]1

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 24758Sodium hydrideHCID 14476399HCID 14476399, compoundHCID 14476400HCID 14476400, compound

Product 1

HCID 20065665HCID 20065665, compoundYield 77.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent2×HCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

A solution of 3-dimethylamino-1-isoindolinone (11.7 g) in anhydrous dimethylformamide (300 cc) is added to a suspension of sodium hydride (as a 50% suspension in oil) (3.5 g) in anhydrous dimethylformamide (150 cc) at a temperature close to 20° C. in the course of 30 minutes, and agitation is continued for 1 hour. Then, a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-bromopropane (20.5 g) in dimethylformamide (150 cc) is added in the course of 15 minutes, and agitation is continued for a further 20 hours. The solution obtained is evaporated to dryness under reduced pressure (1 mm mercury; 0.1 kPa). The residue obtained is dissolved in methylene chloride (350 cc) and washed with distilled water (3×150 cc). The organic extract is dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methylene chloride (50 cc) and poured onto silica (1000 g) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (95-5 by volume). The first 2300 cc are eliminated and the eluate corresponding to the next 1500 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is dissolved in methyl ethyl ketone (80 cc). A solution of oxalic acid (1.9 g) in methyl ethyl ketone (20 cc) is added and agitation is continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 7.6 g of 3-dimethylamino-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 159° C.

Workup

  1. customclose to 20° C. in the course of 30 minutes, and agitation
  2. waitis continued for a further 20 hours
  3. customThe solution obtained
  4. customis evaporated to dryness under reduced pressure (1 mm mercury; 0.1 kPa)
  5. customThe residue obtained
  6. washwashed with distilled water (3×150 cc)
  7. extractionThe organic extract
  8. dry with materialis dried over anhydrous magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  11. customThe residue obtained
  12. additionpoured onto silica (1000 g)
  13. washElution
  14. additionis carried out with a mixture of methylene chloride and methanol (95-5 by volume)
  15. concentrationthe eluate corresponding to the next 1500 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa)
  16. customThe residue obtained
  17. waitagitation is continued for 1 hour at a temperature
  18. customclose to 20° C
  19. customThe precipitate formed
  20. customis separated by filtration

Sources & evidence

ORD record
ord-87725b08f7fe4d2696123c94b3e65976
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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