Oxalic Acid → HCID 20065666, compound

HRID 359127Notes

Reaction equation

HRID 359127 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](O)([CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:24]3=[O:40])[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:53]([OH:58])(=[O:57])[C:54]([OH:56])=[O:55]>C(Cl)Cl.O1CCCC1.C(#N)C>[C:53]([OH:58])(=[O:57])[C:54]([OH:56])=[O:55].[CH2:32]([CH:31]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:40])[N:23]1[CH2:22][CH2:21][CH2:20][N:17]1[CH2:16][CH:15]=[C:14]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:19][CH2:18]1)[C:33]1[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 14476391HCID 14476391, compound

Product 1

HCID 20065666HCID 20065666, compoundYield 115.4%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

75 cc of trifluoroacetic acid is added in the course of 45 minutes to 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-3-hydroxy-3-benzyl-1-isoindolinone (15.2 g) and sodium cyanoborohydride (4.6 g) cooled to a temperature close to -25° C. Agitation is continued for 4 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 (200 cc). The aqueous phase is extracted with methylene chloride (4×150 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 (3.1 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), and 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 dissolved in acetonitrile (20 cc). A solution of oxalic acid (0.7 g) in acetonitrile (20 cc) is added and agitation is continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration and recrystallized from boiling methanol (280 cc). 4.6 g of 3-benzyl-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 219° 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 (200 cc)
  5. extractionThe aqueous phase is extracted with methylene chloride (4×150 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. waitagitation is continued for 1 hour at a temperature
  23. customclose to 20° C
  24. customThe precipitate formed
  25. customis separated by filtration
  26. customrecrystallized

Sources & evidence

ORD record
ord-1d17044806644ab98db8a5a6fd9daeab
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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