Triethylamine → 3-[(N-[5,5-dimethyl-1-pyrrolin-2-yl)anilino]methyl]indole hydrochloride

HRID 2072175Notes

Reaction equation

HRID 2072175 reaction equation
P(Cl)(Cl)([Cl:3])=O.[NH:6]([CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:23][C:24]1([CH3:30])[NH:28][C:27](=O)[CH2:26][CH2:25]1.C(N(CC)CC)C>ClCCCl>[ClH:3].[CH3:23][C:24]1([CH3:30])[N:28]=[C:27]([N:6]([CH2:13][C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 107042713-(Anilinomethyl)indoleHCID 111262105,5-Dimethylpyrrolidin-2-one

Product 1

HCID 705301023-[(N-[5,5-dimethyl-1-pyrrolin-2-yl)anilino]methyl]indole hydrochloride

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

Phosphorus oxychloride (7.67 g., 0.05 mole) in 20 ml. of 1,2-dichloroethane is added rapidly to 3-(anilinomethyl)indole (11.1 g., 0.05 mole), 5,5-dimethyl-2-pyrrolidinone (5.66 g., 0.05 mole) and triethylamine (5.06 g., 0.05 mole) in 80 ml. of 1,2-dichloroethane at ice bath temperature. After stirring the mixture for about 15 min., the ice bath is removed and stirring continued at room temperature for 16 hr. Workup of the reaction mixture is as follows. The mixture is quenched in 100 ml. of 10% sodium hydroxide and crushed ice and the organic layer separated. The organic layer is extracted with 100 ml. of 1.5 N hydrochloric acid and then with 100 ml. of water. After washing the combined extracts with ether and making basic with 10% sodium hydroxide, a solid precipitates which is collected and crystallized from ethyl acetate, yield 3.2 g., m.p. 124°-126° C. of free base product. The dichloroethane fraction is dried over magnesium sulfate and concentrated in vacuum and the residue (10.4 g.) triturated with water and filtered. The aqueous filtrate is made basic with sodium hydroxide providing a second free base fraction, yield 3.1 g., m.p. 125°-127° C. The two free base fractions are combined, dissolved in ethanol and treated with ethanolic hydrogen chloride affording 3.7 g., m.p. 185°-185.5° C. (dec.) (corr.) of analytically pure 3-[(N-(5,5-dimethyl-1-pyrrolin-2-yl)anilino]methyl]indole hydrochloride.

Workup

  1. customthe ice bath is removed
  2. stirringstirring
  3. waitcontinued at room temperature for 16 hr
  4. customThe mixture is quenched in 100 ml
  5. customof 10% sodium hydroxide and crushed ice
  6. customthe organic layer separated
  7. extractionThe organic layer is extracted with 100 ml
  8. washAfter washing the combined extracts with ether
  9. customa solid precipitates which
  10. customis collected
  11. customcrystallized from ethyl acetate, yield 3.2 g
  12. dry with materialThe dichloroethane fraction is dried over magnesium sulfate
  13. concentrationconcentrated in vacuum
  14. customthe residue (10.4 g.) triturated with water
  15. filtrationfiltered
  16. dissolutiondissolved in ethanol
  17. additiontreated with ethanolic hydrogen chloride affording 3.7 g

Sources & evidence

ORD record
ord-4a205b3293d243868bc38401d106d71b
Source dataset
uspto-grants-1977_09
Patent number
US04049714

Reaction notes

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