Aniline → HCID 14476375, compound

HRID 359112Notes

Reaction equation

HRID 359112 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](O)[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.[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1(C)C(C)=CC=CC=1.C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:28]1([NH:27][CH:24]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17](=[O:26])[N:16]2[CH2:15][CH2:14][CH2:13][N:10]2[CH2:11][CH:12]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 2

HCID 6115AnilineHCID 14476373HCID 14476373, compound

Product 1

HCID 14476375HCID 14476375, compoundYield 93.8%

Reagents, catalysts & solvents 3

HCID 6101p-Toluenesulfonic acidCatalystHCID 6344DichloromethaneSolventHCID 7237O-XyleneSolvent

Procedure

Para-toluenesulphonic acid (50 mg) is added to an agitated solution of 2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-3-hydroxy-1-isoindolinone (5 g) and aniline (1.7 g) in xylene (100 cc) at a temperature close to 20° C. in a Dean Stark apparatus. Agitation is continued for 9 hours at a temperature close to 135° C. After cooling to a temperature close to 20° C., the solution is washed with aqueous sodium bicarbonate solution (2×50 cc) then with distilled water (2×30 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 80° C. The residue obtained is dissolved in methylene chloride (10 cc) and poured onto silica (100 g) contained in a column of 2 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (95-5 by volume) (1300 cc) and the corresponding eluate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). The precipitate formed is recrystallized from boiling acetonitrile (30 cc). 5.7 g of 3-phenylamino-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone are obtained, melting at 119° C.

Workup

  1. customclose to 20° C. in a Dean Stark apparatus
  2. customclose to 135° C
  3. temperatureAfter cooling to a temperature
  4. customclose to 20° C.
  5. washthe solution is washed with aqueous sodium bicarbonate solution (2×50 cc)
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 80° C
  9. customThe residue obtained
  10. additionpoured onto silica (100 g)
  11. washElution
  12. additionis carried out with a mixture of methylene chloride and methanol (95-5 by volume) (1300 cc)
  13. concentrationthe corresponding eluate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa)
  14. customThe precipitate formed
  15. customis recrystallized

Sources & evidence

ORD record
ord-ab2d8c1777544a8f9b601f859aa8d256
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Reaction notes

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