Sodium amide → Indan-2-yl-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]phenylamine

HRID 538666Notes

Reaction equation

HRID 538666 reaction equation
[NH2-].[Na+].[CH2:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH:4]1[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl.Cl[CH2:21][CH2:22][CH:23]1[CH2:27][CH2:26][CH2:25][N:24]1[CH3:28]>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:3][CH:4]1[N:12]([CH2:21][CH2:22][CH:23]1[CH2:27][CH2:26][CH2:25][N:24]1[CH3:28])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 24533Sodium amideHCID 118068N-phenylindan-2-amineHCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)

Product 1

HCID 68180914Indan-2-yl-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]phenylamine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of sodamide (256 mg, 6.58 mmol) in toluene (10 mL) was added a solution of indan-2-yl-phenyl-amine (7; 1.0 g, 4.78 mmol) in toluene (5 mL) at 0° C. The reaction mixture was stirred at rt for 3 hours. A solution of 2-(2-chloroethyl)-1-methyl-pyrrolidine hydrochloride (18; 0.808 g, 4.39 mmol) in toluene (5 mL) was added to the reaction mixture and the resulting mixture was refluxed for 16 hours. The reaction mixture was diluted with EtOAc and washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography on neutral alumina eluting with 0.8% methanol-DCM to provide compound 19.

Workup

  1. temperaturethe resulting mixture was refluxed for 16 hours
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by column chromatography on neutral alumina eluting with 0.8% methanol-DCM

Sources & evidence

ORD record
ord-fbb359dbead142639fb4820ef62bcded
Source dataset
uspto-grants-2014_10
Patent number
US08865741B2

Reaction notes

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