Hydrochloric Acid → HCID 13324718, compound

HRID 371490Notes

Reaction equation

HRID 371490 reaction equation
[N:1]1([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[ClH:18].[OH-].[Na+].CCOCC>O1CCCC1>[ClH:18].[N:1]1([C:10]2[CH:17]=[CH:16][C:13]([CH2:14][NH2:15])=[CH:12][CH:11]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 13324709HCID 13324709, compound

Product 1

HCID 13324718HCID 13324718, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 12.06 g (54.8 mmole) of 4-(1-indolinyl)benzonitrile of Example 2a in 62 ml tetrahydrofuran (THF) was added dropwise to a rapidly stirred ice cold solution of BH3 in THF (181 ml of 0.93M solution, 3.07 equiv. 168.4 mmole) under nitrogen. After heating at reflux for 1.5 hours, the solution was permitted to cool to room temperature and stand overnight. The ice cold reaction mixture was then treated dropwise with 6M aq. HCl (100 ml), heated at reflux for 40 minutes, cooled to 0° C., and made basic using solid NaOH. The resulting aqueous phase was extracted with ether and the combined organic portions (100 ml total) were washed with water (300 ml), twice with brine (300 ml portions) dried (Na2SO4) and concentrated to afford 13.2 g of crude free base. A solution of 7.5 g (33.4 mmole) of crude free base in 200 ml 1:1 ethanol-ether was treated with 50 ml of ethanolic HCl. 200 ml dry ether was added and the resulting solid was filtered, washed with dry ether, and dried thus giving 5.9 g (67.7%) of crude product. Recrystallization from hot ethanol-ether (charcoal) afforded 2.98 g of pure 4-(1-indolinyl)benzenemethanamine hydrochloride, m.p. 251.5°-252.5° C.

Workup

  1. temperatureAfter heating
  2. temperatureat reflux for 1.5 hours
  3. temperatureheated
  4. temperatureat reflux for 40 minutes
  5. temperaturecooled to 0° C.
  6. extractionThe resulting aqueous phase was extracted with ether
  7. washthe combined organic portions (100 ml total) were washed with water (300 ml), twice with brine (300 ml portions)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customto afford 13.2 g of crude free base
  11. filtrationthe resulting solid was filtered
  12. washwashed with dry ether
  13. customdried thus
  14. customgiving 5.9 g (67.7%) of crude product
  15. customRecrystallization from hot ethanol-ether (charcoal)

Sources & evidence

ORD record
ord-5f66a1e2f5334ec49a4d916ab8a70f59
Source dataset
uspto-grants-1985_07
Patent number
US04532333

Reaction notes

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