Oxalic Acid → HCID 20065664, compound

HRID 359118Notes

Reaction equation

HRID 359118 reaction equation
[CH3:1][NH:2][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:15]1([C:21]2[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][CH2:29]Br)[CH2:25][CH:26]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:31]([OH:36])(=[O:35])[C:32]([OH:34])=[O:33]>CN(C)C=O.C(Cl)Cl.C(C(C)=O)C>[C:31]([OH:36])(=[O:35])[C:32]([OH:34])=[O:33].[CH3:1][NH:2][CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[N:4]1[CH2:29][CH2:28][CH2:27][N:24]1[CH2:23][CH:22]=[C:21]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 24758Sodium hydrideHCID 13319447HCID 13319447, compoundHCID 14476400HCID 14476400, compound

Product 1

HCID 20065664HCID 20065664, compoundYield 83.1%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 3-methylamino-1-isoindolinone (6.8 g) in anhydrous dimethylformamide (200 cc) is added to a suspension of sodium hydride (as a 50% suspension in oil) (2.2 g) in anhydrous dimethylformamide (100 cc) at a temperature close to 20° C. in the course of 15 minutes and agitation is continued for 1 hour. Then, a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-bromopropane (13 g) in dimethylformamide (100 cc) is added in the course of 10 minutes, and agitation is continued for a further 20 hours. The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa). The residue obtained is dissolved in methylene chloride (500 cc) and washed with distilled water (3×500 cc). The organic phase 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 (20 cc) and poured onto silica (750 g ) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume). The first 3750 cc are eliminated and the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is dissolved in methyl ethyl ketone (50 cc). A solution of oxalic acid (1.2 g) in methyl ethyl ketone (20 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 5 g of 3-methylamino-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 122° C.

Workup

  1. customclose to 20° C. in the course of 15 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 Hg; 0.1 kPa)
  5. customThe residue obtained
  6. washwashed with distilled water (3×500 cc)
  7. dry with materialThe organic phase is dried over anhydrous magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  10. customThe residue obtained
  11. additionpoured onto silica (750 g )
  12. washElution
  13. additionis carried out with a mixture of methylene chloride and methanol (92-8 by volume)
  14. concentrationthe eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa)
  15. customThe residue obtained
  16. waitagitation continued for 1 hour at a temperature
  17. customclose to 20° C
  18. customThe precipitate formed
  19. customis separated by filtration

Sources & evidence

ORD record
ord-07d2512739f746929497278bb9f5d8a0
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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