Ammonia → HCID 20065675, compound

HRID 359109Notes

Reaction equation

HRID 359109 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][N:17]3[CH:25]([OH:26])[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]3=[O:27])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.N.[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36]>CO.C(Cl)Cl.C(#N)C>[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36].[CH3:34][O:27][CH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:25](=[O:26])[N:17]1[CH2:16][CH2:15][CH2:14][N:11]1[CH2:10][CH2:9][N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 971Oxalic AcidHCID 1118Sulfuric AcidHCID 14476397HCID 14476397, compound

Product 1

HCID 20065675HCID 20065675, compoundYield 141.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

The same procedure is followed as in Example 2, starting from an agitated solution of 2-[3-(4-(4-fluorophenyl)-1-piperazinyl)propyl]-3-hydroxy-1 -isoindolinone (6.8 g) in methanol (170 cc) to which 33.5 cc of concentrated sulphuric acid is added at a temperature close to 20° C. in the course of 15 minutes. Agitation is continued for 5 hours at a temperature close to 65° C. After cooling the solution to a temperature close to 0° C., 83 cc of a 33% aqueous solution of ammonia is added in the course of 1 hour. The precipitate formed is filtered and washed with methanol (50 cc). The filtrate is diluted with distilled water (200 cc) and a 33% aqueous solution of ammonia (50 cc) and extracted with methylene chloride (3×200 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 is poured onto silica (500 g) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (99-1 by volume). The first 300 cc are eliminated and the next 3500 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C. The residue obtained is dissolved in acetonitrile (50 cc). A solution of oxalic acid (1.1 g) in acetonitrile (25 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 4.1 g of 3-methoxy-2-[3-(4-(4-fluorophenyl)-1-piperazinyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 177° C.

Workup

  1. additionis added at a temperature
  2. customclose to 20° C. in the course of 15 minutes
  3. customclose to 65° C
  4. temperatureAfter cooling the solution to a temperature
  5. customclose to 0° C.
  6. customThe precipitate formed
  7. filtrationis filtered
  8. washwashed with methanol (50 cc)
  9. additionThe filtrate is diluted with distilled water (200 cc)
  10. extractiona 33% aqueous solution of ammonia (50 cc) and extracted with methylene chloride (3×200 cc)
  11. dry with materialdried over anhydrous magnesium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  14. customThe residue obtained
  15. additionthe solution is poured onto silica (500 g)
  16. washElution
  17. additionis carried out with a mixture of methylene chloride and methanol (99-1 by volume)
  18. customthe next 3500 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  19. customThe residue obtained
  20. waitagitation continued for 1 hour at a temperature
  21. customclose to 20° C
  22. customThe precipitate formed
  23. customis separated by filtration

Sources & evidence

ORD record
ord-da64d218e5ae46f18374300958e56e98
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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