Hydrochloric Acid → Benzenemethanamine, 2-(2,3-dihydro-1H-indol-1-yl)-, hydrochloride (1:1)

HRID 371488Notes

Reaction equation

HRID 371488 reaction equation
[N:1]1([C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[C:12]#[N:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[ClH:18].[OH-].[Na+]>O1CCCC1.CCOCC>[ClH:18].[N:1]1([C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[CH2:12][NH2:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 133247142-(2,3-Dihydro-1H-indol-1-yl)benzonitrile

Product 1

HCID 13324720Benzenemethanamine, 2-(2,3-dihydro-1H-indol-1-yl)-, hydrochloride (1:1)Yield 67.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 17.18 g (0.078 mole) of 2(1-indolinyl)benzonitrile of Example 1a in 150 ml dry tetrahydrofuran (THF) was added dropwise to a rapidly stirred ice cold solution of BH3 in THF (236 ml of 1M solution; 0.236 mole) under nitrogen. At the end of the addition the resultant solution was permitted to warm to room temperature and stir for 3 hours and then heated at reflux for 50 minutes. The product was then cooled to 0° C., treated dropwise with 6N HCl (100 ml), and permitted to stand overnight (about 16 hours) at room temperature. The reaction mixture was cooled to 0° C. and made basic using solid NaOH. The resulting aqueous layer was extracted with ether (200 ml) and the combined organic portions were washed twice with brine (200 ml portions), dried over K2CO3, and concentrated to afford 21.1 g of crude free base. The free amine was dissolved in dry ether (300 ml), cooled to 0° C., and treated with gaseous HCl. The resulting salt was filtered, washed with dry ether (300 ml), and dried under vacuum at 40° C. thus affording 19.25 g (94.4%) of crude salt, m.p. 226°-228° C. Recrystallization of 15.59 g of the crude salt from methanol-ether afforded 10.49 g (67.3% recovery) of 2-(1-indolinyl) benzenemethanamine hydrochloride, m.p. 231°-232° C.

Workup

  1. temperatureheated
  2. temperatureat reflux for 50 minutes
  3. temperatureThe product was then cooled to 0° C.
  4. waitto stand overnight
  5. custom(about 16 hours)
  6. customat room temperature
  7. temperatureThe reaction mixture was cooled to 0° C.
  8. extractionThe resulting aqueous layer was extracted with ether (200 ml)
  9. washthe combined organic portions were washed twice with brine (200 ml portions)
  10. dry with materialdried over K2CO3
  11. concentrationconcentrated
  12. customto afford 21.1 g of crude free base
  13. temperaturecooled to 0° C.
  14. filtrationThe resulting salt was filtered
  15. washwashed with dry ether (300 ml)
  16. customdried under vacuum at 40° C.
  17. customthus affording 19.25 g (94.4%) of crude salt, m.p. 226°-228° C
  18. customRecrystallization of 15.59 g of the crude salt from methanol-ether

Sources & evidence

ORD record
ord-d0f8354959034acc9d666bd4ecce57b9
Source dataset
uspto-grants-1985_07
Patent number
US04532333

Reaction notes

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