Hydrochloric Acid → 3-[[N-(1-pyrrolin-2-yl)anilino]methyl]indole hydrochloride

HRID 616184Notes

Reaction equation

HRID 616184 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.[NH:23]1[CH2:27][CH2:26][CH2:25][C:24]1=O.C(N(CC)CC)C.Cl>C(O)C.O.ClCCCl>[ClH:3].[N:23]1[CH2:27][CH2:26][CH2:25][C:24]=1[N: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:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 120252-PyrrolidoneHCID 24813Phosphorus oxychlorideHCID 107042713-(Anilinomethyl)indole

Product 1

HCID 205097193-[[N-(1-pyrrolin-2-yl)anilino]methyl]indole hydrochloride

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Phosphorus oxychloride (7.67 g., 0.05 mole) is added in one portion to a stirred mixture of 3-(anilinomethyl)indole (11.1 g., 0.05 mole), 2-pyrrolidinone (4.26 g., 0.05 mole) and triethylamine (5.06 g., 0.05 mole) in 100 ml. of 1,2-dichloroethane at ice bath temperature. Stirring is continued at that temperature for 15 min. and then at room temperature for about 16 hr. After quenching in crushed ice and aqueous sodium hydroxide, the reaction mixture is filtered providing 2.5 g., of solid free base m.p. 115°-117° C. The filtrate is worked up according to the method of Example 34 by extracting the dichloroethane layer with hydrochloric acid and subsequently extracting the acid extract with ether and then making basic with sodium hydroxide. Ether extraction of the basic aqueous mixture with ether and concentrating the dried ethereal extract affords a second free base fraction, 4.1 g., melting at 118°-120° C. The free base fractions are combined and a 5.1 g. sample converted to the hydrochloride salt in ethanol by treatment with ethanolic hydrogen chloride. Concentration of the acidic ethanolic solution provides a residue which is taken up in water and filtered from a small amount of solid. The filtrate is cooled and made basic with 10% aqueous sodium hydroxide affording the free base which is collected, 3.1 ., m.p. 118°-120 C. The reprepared free base is then converted to the hydrochloride salt in the usual manner ethanol by treatment with ethanolic hydrogen chloride. Addition of ether to the ethanolic solution yields analytically pure 3 -[[N-(1-pyrrolin-2-yl)anilino)methyl]indole hydrochloride, 2.6 g., m.p. 163.5°-166.5° C. (corr.)

Workup

  1. waitat room temperature for about 16 hr
  2. customAfter quenching in crushed ice
  3. filtrationaqueous sodium hydroxide, the reaction mixture is filtered
  4. customproviding 2.5 g
  5. extractionby extracting the dichloroethane layer with hydrochloric acid
  6. extractionsubsequently extracting the acid
  7. extractionextract with ether
  8. extractionEther extraction of the basic aqueous mixture with ether
  9. concentrationconcentrating the dried ethereal
  10. extractionextract
  11. customaffords a second free base fraction, 4.1 g
  12. customConcentration of the acidic ethanolic solution provides a residue which
  13. filtrationfiltered from a small amount of solid
  14. temperatureThe filtrate is cooled
  15. customis collected
  16. additionAddition of ether to the ethanolic solution

Sources & evidence

ORD record
ord-8c70cc6e594f4203aa6292cc6b77c145
Source dataset
uspto-grants-1978_02
Patent number
US04072675

Reaction notes

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