Oxalic Acid → 3-Methyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate

HRID 359125Notes

Reaction equation

HRID 359125 reaction equation
[C:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)(=O)[CH3:2].[C:13]1([C:19]2[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][CH2:27][NH2:28])[CH2:23][CH:24]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl.C1(C2CCN(CCCN)CC=2)C=CC=CC=1.C([BH3-])#N.[Na+].[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52]>C(#N)C.C(C(C)=O)C>[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52].[CH3:2][CH:1]1[C:4]2[C:5](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:6](=[O:8])[N:28]1[CH2:27][CH2:26][CH2:25][N:22]1[CH2:21][CH:20]=[C:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:24][CH2:23]1

Participants

8

Reactant 5

HCID 971Oxalic AcidHCID 684742-Acetylbenzoic acidHCID 5003444Sodium cyanoborohydrideHCID 14476401[3-(4-Phenyl-3,6-dihydropyridin-1(2H)-yl)propyl]amineHCID 20065674HCID 20065674, compound

Product 1

HCID 200656693-Methyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

2.5 g of 2-acetylbenzoic acid is added to a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-aminopropane (7.8 g) in acetonitrile (90 cc) at a temperature close to 20° C. in the course of 10 minutes. Agitation is continued for 4 hours then 7.6 g of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-aminopropane hydrochloride is added in the course of 30 minutes. Then 1.2 g of sodium cyanoborohydride is added to the suspension obtained, in the course of 5 minutes. Agitation is continued for 16 hours. The suspension is filtered and the precipitate washed with acetonitrile (20 cc). The organic extracts are combined, diluted with methylene chloride (200 cc) then washed with distilled water (120 cc), dried over anhydrous magnesium sulphate, treated with animal charcoal, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is poured onto alumina (750 g) contained in a column of 6 cm diameter. Elution is carried out with ethyl acetate (1000 cc) and the corresponding eluates are eliminated. Then elution is carried out with a mixture of ethyl acetate and methanol (98-2 by volume) (1000 cc) and the corresponding eluates are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in methyl ethyl ketone (20 cc). A solution of oxalic acid (0.3 g) in methyl ethyl ketone (10 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration and recrystallized from boiling acetonitrile (80 cc). 0.9.g of 3-methyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 147° C.

Workup

  1. customclose to 20° C. in the course of 10 minutes
  2. customobtained, in the course of 5 minutes
  3. waitAgitation is continued for 16 hours
  4. filtrationThe suspension is filtered
  5. washthe precipitate washed with acetonitrile (20 cc)
  6. additiondiluted with methylene chloride (200 cc)
  7. washthen washed with distilled water (120 cc)
  8. dry with materialdried over anhydrous magnesium sulphate
  9. additiontreated with animal charcoal
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  12. customThe residue obtained
  13. additionis poured onto alumina (750 g)
  14. washElution
  15. washThen elution
  16. additionis carried out with a mixture of ethyl acetate and methanol (98-2 by volume) (1000 cc)
  17. customthe corresponding eluates are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  18. customThe residue obtained
  19. waitagitation continued for 1 hour at a temperature
  20. customclose to 20° C
  21. customThe precipitate formed
  22. customis separated by filtration
  23. customrecrystallized

Sources & evidence

ORD record
ord-44717d22d2ee4b699699022ca00b7ff1
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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