Ammonia → HCID 20065653, compound

HRID 359128Notes

Reaction equation

HRID 359128 reaction equation
[OH:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)[CH2:17][CH2:16]1.S(=O)(=O)(O)O.N.[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36]>CO.C(Cl)Cl.C(C(C)=O)C>[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36].[CH3:34][O:11][CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:22]=[CH:23][C:24]([OH:27])=[CH:25][CH:26]=2)[CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 971Oxalic AcidHCID 1118Sulfuric AcidHCID 14476396HCID 14476396, compound

Product 1

HCID 20065653HCID 20065653, compoundYield 66.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

The same procedure is followed as in Example 2, but starting from an agitated solution of 3-hydroxy-2-[3-(4-(4-hydroxyphenyl)-1-piperazinyl)propyl]-1-isoindolinone (4.6 g) in methanol (115 cc), to which 22.7 cc of concentrated sulphuric acid is added in the course of 15 minutes and at a temperature close to 20° C. Agitation is continued for 5 hours at a temperature close to 65° C. After cooling the solution to a temperature close to 0° C., 57 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 (4×100 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 6 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (97-3 by volume). The first 800 cc are eliminated and the next 3000 cc 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 (35 cc). A solution of oxalic acid (0.8 g) in methyl ethyl ketone (20 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 (200 cc). 1.4 g of 3-methoxy-2-[3-(4-(4-hydroxyphenyl)-1-piperazinyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 147° C.

Workup

  1. additionis added in the course of 15 minutes and at a temperature
  2. customclose to 20° C
  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 (4×100 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 (97-3 by volume)
  18. customthe next 3000 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
  24. customrecrystallized

Sources & evidence

ORD record
ord-b9d91846020444af87d4cc616d77c522
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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