Methanethiol → 3-Methylthio-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate

HRID 359124

Reaction equation

HRID 359124 reaction equation
[CH3:1][SH:2].[CH:3]([C:5]1[CH:14]=[CH:13][CH:12]=[CH:11][C:6]=1[C:7]([O:9]C)=O)=O.[C:15]1([C:21]2[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][CH2:29][NH2:30])[CH2:25][CH:26]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[Na+].[C:33]([OH:38])(=[O:37])[C:34]([OH:36])=[O:35]>O1CCCC1.C(OCC)(=O)C.C(C(C)=O)C>[C:33]([OH:38])(=[O:37])[C:34]([OH:36])=[O:35].[CH3:1][S:2][CH:3]1[C:5]2[C:6](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:7](=[O:9])[N:30]1[CH2:29][CH2:28][CH2:27][N:24]1[CH2:23][CH:22]=[C:21]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:26][CH2:25]1

Participants

9

Reactant 5

HCID 878MethanethiolHCID 971Oxalic AcidHCID 14798Sodium HydroxideHCID 243003Methyl 2-formylbenzoateHCID 14476401[3-(4-Phenyl-3,6-dihydropyridin-1(2H)-yl)propyl]amine

Product 1

HCID 200656773-Methylthio-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate

Reagents, catalysts & solvents 3

HCID 6569Methyl Ethyl KetoneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

5 cc of methylmercaptan is added to a solution of methyl 2-formylbenzoate (3.6 g) and 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-aminopropane (9.6 g)in tetrahydrofuran (255 cc) in an autoclave, at a temperature close to -20° C. in the course of 5 minutes. The solution is heated to a temperature close to 60° C. for 4 hours. After cooling to a temperature close to 20° C., the solution is poured into 1N sodium hydroxide (300 cc) and washed with distilled water (3×500 cc). The organic extract is 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 ethyl acetate (20 cc) and poured onto silica (750 g) contained in a column of 8 cm diameter. Elution is carried out with ethyl acetate. The first 3400 cc are eliminated and the next 3100 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methyl ethyl ketone (70 cc). A solution of oxalic acid (1.7 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. 5.9 g of 3-methylthio-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 169° C.

Workup

  1. customclose to -20° C. in the course of 5 minutes
  2. temperatureThe solution is heated to a temperature
  3. customclose to 60° C. for 4 hours
  4. temperatureAfter cooling to a temperature
  5. customclose to 20° C.
  6. washwashed with distilled water (3×500 cc)
  7. extractionThe organic extract
  8. dry with materialis dried over anhydrous magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  11. customThe residue obtained
  12. additionpoured onto silica (750 g)
  13. washElution
  14. customthe next 3100 cc are evaporated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  15. customThe residue obtained
  16. customclose to 20° C
  17. customThe precipitate formed
  18. customis separated by filtration

Sources & evidence

ORD record
ord-e71c2da52b9243b999745dc6f52d10e8
Source dataset
uspto-grants-1991_03
Patent number
US04999355

Linked notes

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