Hydrochloric Acid → Linopirdine

HRID 1382493Notes

Reaction equation

HRID 1382493 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:9]2=[O:23])=[CH:3][CH:2]=1.[BH4-].[Na+].[OH-].[Na+].Cl>CO.O>[N:1]1[CH:2]=[CH:3][C:4]([CH2:7][C:8]2([CH2:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:9]2=[O:23])=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 538855951-Phenyl-3-[(pyridin-4-yl)methylidene]-1,3-dihydro-2H-indol-2-one

Product 1

HCID 3932LinopirdineYield 147.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A slurry of 3-(4-pyridinylmethylidene)-1-phenylindolin-2-one (80 g, 0.268M) in methanol (600 mL) was cooled to 6°. Sodium borohydride pellets (0.2 g each, 3.19 g total 0.084M) were added over 20 minutes with gentle cooling. The mixture was stirred for 50 minutes, cooled to 7°, and 10N sodium hydroxide (64 mL, 0.64M) added over 11 minutes. A solution of 4-picolychloride hydrochloride (4.85 g, 0.296M) in water (160 mL) was then added over 28 minutes while maintaining a temperature of 10°-15°. Cooling was then removed, and 10N sodium hydroxide (80 mL, 0.8M) added over 10 minutes. The mixture was stirred for 2 hours and then water (580 mL) added over 45 minutes. The slurry was cooled to 10°-15°, stirred for 10 minutes, and the solids collected by filtration. The solids were then reslurried in water (450 mL), filtered, and washed with water. Drying in a vacuum oven at 85°-95° yielded 89.4 g (85%) crude title compound. This crude product (85 g) was recrystallized in isopropanol and water to yield 77.3 g of the title compound (90% recovery). M.P.: =186°-188°.

Workup

  1. additionwere added over 20 minutes with gentle cooling
  2. temperaturecooled to 7°
  3. temperaturewhile maintaining a temperature of 10°-15°
  4. temperatureCooling
  5. customwas then removed
  6. addition10N sodium hydroxide (80 mL, 0.8M) added over 10 minutes
  7. stirringThe mixture was stirred for 2 hours
  8. additionwater (580 mL) added over 45 minutes
  9. temperatureThe slurry was cooled to 10°-15°
  10. stirringstirred for 10 minutes
  11. filtrationthe solids collected by filtration
  12. filtrationfiltered
  13. washwashed with water
  14. customDrying in a vacuum oven at 85°-95°
  15. customyielded 89.4 g (85%) crude title compound
  16. customThis crude product (85 g) was recrystallized in isopropanol

Sources & evidence

ORD record
ord-20fece0df1c946719f43c1784f9c4546
Source dataset
uspto-grants-1989_02
Patent number
US04806651

Reaction notes

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