Ammonia → HCID 20065651, compound

HRID 359107Notes

Reaction equation

HRID 359107 reaction equation
S(=O)(=O)(O)O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH2:14][CH2:15][N:16]([CH2:19][CH2:20][CH2:21][N:22]3[CH:30]([OH:31])[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[C:23]3=[O:32])[CH2:17][CH:18]=2)=[CH:9][CH:8]=1.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:32][CH:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:30](=[O:31])[N:22]1[CH2:21][CH2:20][CH2:19][N:16]1[CH2:15][CH:14]=[C:13]([C:10]2[CH:11]=[CH:12][C:7]([F:6])=[CH:8][CH:9]=2)[CH2:18][CH2:17]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 971Oxalic AcidHCID 1118Sulfuric AcidHCID 14476370HCID 14476370, compound

Product 1

HCID 20065651HCID 20065651, compoundYield 153.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

28.5 cc of concentrated sulphuric acid is added to an agitated solution of 2-[3-(4-(4-fluorophenyl)-1,2,3,6-tetrahydro-1-pyridyl)propyl]-3-hydroxy-1-isoindolinone (5.7 g) in methanol (145 cc) at a temperature close to 20° C. in the course of 10 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., 70 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 (10 cc) and the solution poured onto silica (550 g) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (90-10 by volume). The first 900 cc are eliminated and the following 200 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 (10 cc). A solution of oxalic acid (0.6 g) in methyl ethyl ketone (5 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 2.4 g of 3-methoxy-2-[3-(4-(4-fluorophenyl)-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are obtained, melting at 139° C.

Workup

  1. customclose to 20° C. in the course of 10 minutes
  2. customclose to 65° C
  3. temperatureAfter cooling the solution to a temperature
  4. customclose to 0° C.
  5. customThe precipitate formed
  6. filtrationis filtered
  7. washwashed with methanol (50 cc)
  8. additionThe filtrate is diluted with distilled water (200 cc)
  9. extractiona 33% aqueous solution of ammonia (50 cc) and extracted with methylene chloride (3×200 cc)
  10. dry with materialdried over anhydrous magnesium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  13. customThe residue obtained
  14. additionthe solution poured onto silica (550 g)
  15. washElution
  16. additionis carried out with a mixture of methylene chloride and methanol (90-10 by volume)
  17. customthe following 200 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 50° C
  18. customThe residue obtained
  19. waitagitation continued for 1 hour at a temperature
  20. customclose to 20° C
  21. customThe precipitate formed
  22. customis separated by filtration

Sources & evidence

ORD record
ord-559409b0f8d4406ebcd10f66a5d819cf
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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