Ammonia → HCID 20065670, compound

HRID 359111Notes

Reaction equation

HRID 359111 reaction equation
[C:1]1([C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH2:15][N:16]3[CH:24]([OH:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]3=[O:26])[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)O.N.[C:33]([OH:38])(=[O:37])[C:34]([OH:36])=[O:35]>C(O)C.C(Cl)Cl.C(C(C)=O)C>[C:33]([OH:38])(=[O:37])[C:34]([OH:36])=[O:35].[CH2:33]([O:26][CH:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24](=[O:25])[N:16]1[CH2:15][CH2:14][CH2:13][N:10]1[CH2:9][CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1)[CH3:34]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 971Oxalic AcidHCID 1118Sulfuric AcidHCID 14476373HCID 14476373, compound

Product 1

HCID 20065670HCID 20065670, compoundYield 157.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

The same procedure is followed as in Example 2, but starting from an agitated solution of 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-3-hydroxy-1-isoindolinone (7 g) in ethanol (265 cc) to which 37 cc of concentrated sulphuric acid is added at a temperature close to 20° C. and in the course of 15 minutes. Agitation is continued for 4 hours at a temperature close to 65° C. After cooling the solution to a temperature close to 0° C., 90 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 (70 cc) and extracted with methylene chloride (3×250 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 (30 cc) and 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 (95-5 by volume). The first 1000 cc are eliminated, the next 900 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 (50 cc). A solution of oxalic acid (1.2 g) in methyl ethyl ketone (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. 4.9 g of 3-ethoxy-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 150° C.

Workup

  1. additionis added at a temperature
  2. customclose to 20° C. and 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 (70 cc) and extracted with methylene chloride (3×250 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. additionpoured onto silica (500 g)
  16. washElution
  17. additionis carried out with a mixture of methylene chloride and methanol (95-5 by volume)
  18. customthe next 900 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  19. customThe residue obtained
  20. waitagitation is 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-15c32dd8f1bb4d59a0b452fc777881ac
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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