Oxalic Acid → HCID 20065656, compound

HRID 359115Notes

Reaction equation

HRID 359115 reaction equation
[CH3:1][N:2]([CH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[NH:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H-].[Na+].[C:21]1([C:27]2[CH2:28][CH2:29][N:30]([CH2:33][CH2:34][CH2:35]Br)[CH2:31][CH:32]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:37]([OH:42])(=[O:41])[C:38]([OH:40])=[O:39]>CN(C)C=O.C(Cl)Cl.C(C(C)=O)C>[C:37]([OH:42])(=[O:41])[C:38]([OH:40])=[O:39].[CH3:1][N:2]([CH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[N:10]1[CH2:35][CH2:34][CH2:33][N:30]1[CH2:29][CH:28]=[C:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:32][CH2:31]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 971Oxalic AcidHCID 24758Sodium hydrideHCID 14476398HCID 14476398, compoundHCID 14476400HCID 14476400, compound

Product 1

HCID 20065656HCID 20065656, compoundYield 83.8%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 3-(N-methyl-N-phenylamino)-1-isoindolinone (10 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 (200 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 (13 g) in dimethylformamide (100 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 Hg; 0.1 kPa). The residue obtained is dissolved in methylene chloride (200 cc) and washed with distilled water (3×50 cc). The organic extracts are 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 (40 cc) then poured onto silica (800 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 next 1100 cc are 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 (1.1 g) in methyl ethyl ketone (15 cc) is added, and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 5.4 g of 3-(N-methyl-N-phenylamino)-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are 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 Hg; 0.1 kPa)
  5. customThe residue obtained
  6. washwashed with distilled water (3×50 cc)
  7. dry with materialThe organic extracts are 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. additionthen poured onto silica (800 g)
  12. washElution
  13. additionis carried out with a mixture of methylene chloride and methanol (95-5 by volume)
  14. concentrationthe next 1100 cc are 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-0fabb241dcab425bb33e2d013edd906a
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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