Oxalic Acid → HCID 20065655, compound

HRID 359126Notes

Reaction equation

HRID 359126 reaction equation
FC(F)(F)C(O)=O.[C:8]1([C:14]2[CH2:15][CH2:16][N:17]([CH2:20][CH2:21][CH2:22][N:23]3[C:31]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)(O)[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:24]3=[O:39])[CH2:18][CH:19]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C([BH3-])#N.[Na+].CN(C)CCN(C)C.[C:52]([OH:57])(=[O:56])[C:53]([OH:55])=[O:54]>C(Cl)Cl.O1CCCC1.C(C(C)=O)C>[C:52]([OH:57])(=[O:56])[C:53]([OH:55])=[O:54].[C:33]1([CH:31]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24](=[O:39])[N:23]2[CH2:22][CH2:21][CH2:20][N:17]2[CH2:16][CH:15]=[C:14]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:19][CH2:18]2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

9

Reactant 5

HCID 971Oxalic AcidHCID 6422Trifluoroacetic acidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 5003444Sodium cyanoborohydrideHCID 14476390HCID 14476390, compound

Product 1

HCID 20065655HCID 20065655, compoundYield 41.3%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 6569Methyl Ethyl KetoneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

60 cc of trifluoroacetic acid is added in the course of 45 minutes to 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1pyridyl)propyl]-3-phenyl-3-hydroxy-1-isoindolinone (12.4 g) and sodium cyanoborohydride (3.8 g) cooled to a temperature close to -25° C. Agitation is continued for 2 hours at a temperature close to 20° C. The solution is diluted with methylene chloride (150 cc) then washed with saturated aqueous sodium bicarbonate solution (130 cc). The aqueous phase is extracted with methylene chloride (4×100 cc). The organic extracts are combined, washed with 1N hydrochloric acid solution (3×50 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 dissolved in tetrahydrofuran (150 cc). Tetramethylethylenediamine (4.5 cc) is added and the solution heated to a temperature close to 65° C. for 1 hour. After cooling to a temperature close to 20° C., the solution is diluted with methylene chloride (300 cc), washed with distilled water (5×50 cc). The organic extract is dried over anhydrous magnesium sulphate, filtered and evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is poured onto neutral alumina (750 g) contained in a column of 6 cm diameter. Elution is carried out with a mixture of ethyl acetate and cyclohexane (40-60 by volume) (2000 cc) and the corresponding eluates are eliminated. Elution is then carried out with ethyl acetate (3000 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 (30 cc). A solution of oxalic acid (0.7 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 (240 cc). 1.6 g of 3-phenyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are obtained, melting at 198° C.

Workup

  1. temperaturecooled to a temperature
  2. customclose to -25° C
  3. customclose to 20° C
  4. washthen washed with saturated aqueous sodium bicarbonate solution (130 cc)
  5. extractionThe aqueous phase is extracted with methylene chloride (4×100 cc)
  6. washwashed with 1N hydrochloric acid solution (3×50 cc)
  7. dry with materialdried over anhydrous magnesium sulphate
  8. additiontreated with animal charcoal
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  11. customThe residue obtained
  12. temperaturethe solution heated to a temperature
  13. customclose to 65° C. for 1 hour
  14. temperatureAfter cooling to a temperature
  15. customclose to 20° C.
  16. washwashed with distilled water (5×50 cc)
  17. extractionThe organic extract
  18. dry with materialis dried over anhydrous magnesium sulphate
  19. filtrationfiltered
  20. customevaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  21. customThe residue obtained
  22. additionis poured onto neutral alumina (750 g)
  23. washElution
  24. additionis carried out with a mixture of ethyl acetate and cyclohexane (40-60 by volume) (2000 cc)
  25. washElution
  26. customthe corresponding eluates are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  27. customThe residue obtained
  28. waitagitation continued for 1 hour at a temperature
  29. customclose to 20° C
  30. customThe precipitate formed
  31. customis separated by filtration
  32. customrecrystallized

Sources & evidence

ORD record
ord-b2c552bd8c6845138d5b58c7af00db1f
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

Loading…