Oxalic Acid → HCID 20065667, compound

HRID 359108Notes

Reaction equation

HRID 359108 reaction equation
[C:1]1([C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH2:15][N:16]3[CH:24]([OH:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].CI.[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].[CH3:31][O:26][CH:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24](=[O:25])[N:16]1[CH2:15][CH2:14][CH2:13][N:10]1[CH2:9][CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14476373HCID 14476373, compound

Product 1

HCID 20065667HCID 20065667, compoundYield 147.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

A solution of 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1pyridyl)propyl]-3-hydroxy-1-isoindolinone (5.2 g) in anhydrous dimethyl formamide (50 cc) is added to a suspension of sodium hydride (as a 50% suspension in oil, 0.8 g) in anhydrous dimethylformamide (10 cc) at a temperature close to 20° C. in the course of 15 minutes, and agitation is continued for 2 hours. Then, 1 cc of methyl iodide is added in the course of 5 minutes and agitation is continued for a further 20 hours. The suspension obtained is poured into distilled water (1000 cc) and extracted with methylene chloride (3×1000 cc). The organic extracts are combined, 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 the solution poured onto silica (300 g) contained in a column of 7 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (98-2 by volume, 1 liter) and the corresponding eluate evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in methyl ethyl ketone (30 cc). A solution of oxalic acid (0.7 g) in methyl ethyl ketone (10 cc) is added and agitation is continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 2.6 g of 3-methoxy-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 160° 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 suspension obtained
  4. additionis poured
  5. distillationinto distilled water (1000 cc)
  6. extractionextracted with methylene chloride (3×1000 cc)
  7. dry with materialdried 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. additionthe solution poured onto silica (300 g)
  12. washElution
  13. additionis carried out with a mixture of methylene chloride and methanol (98-2 by volume, 1 liter)
  14. customthe corresponding eluate evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  15. customThe residue obtained
  16. waitagitation is 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-d9b626991fe84dc08c0013146f4bdc48
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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