Trifluoroacetic acid → 5-Chloro-1'-[trans-3-(4-chlorophenyl)allyl]-3'-methyl-spiro[indoline-3,4'-piperidine]

HRID 1875549Notes

Reaction equation

HRID 1875549 reaction equation
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH:6]=[CH:7][CH2:8][N:9]2[CH2:14][CH2:13][C:12](=[CH:15]OC)[CH:11]([CH3:18])[CH2:10]2)=[CH:4][CH:3]=1.Cl.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29]N)=[CH:25][CH:24]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.[OH-].[NH4+]>C(Cl)(Cl)Cl.ClCCl>[Cl:22][C:23]1[CH:24]=[C:25]2[C:12]3([CH2:13][CH2:14][N:9]([CH2:8]/[CH:7]=[CH:6]/[C:5]4[CH:19]=[CH:20][C:2]([Cl:1])=[CH:3][CH:4]=4)[CH2:10][CH:11]3[CH3:18])[CH2:15][NH:29][C:26]2=[CH:27][CH:28]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 14923Ammonium HydroxideHCID 71600Hydrazine, (4-chlorophenyl)-, hydrochloride (1:1)HCID 688000601-(4-Chlorocinnamyl)-4-[1-methoxy-methylidene]-3-methyl-piperidine

Product 1

HCID 687996445-Chloro-1'-[trans-3-(4-chlorophenyl)allyl]-3'-methyl-spiro[indoline-3,4'-piperidine]Yield 98.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(4-chlorocinnamyl)-4-[1-methoxy-methylidene]-3-methyl-piperidine (1.25 g) and 4-chlorophenylhydrazine hydrochloride (0.85 g) in chloroform (43 ml) was treated with trifluoroacetic acid (4.3 ml) and heated at reflux under argon for 12 hours. The reaction mixture was cooled to room temperature, triethylsilane (3.1 ml) was added and the solution refluxed for 2 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane, neutralised with aqueous ammonium hydroxide, washed with brine, dried (sodium sulphate) and concentrated. The dark residue was purified by silica gel chromatography (cyclohexane:ethyl acetate 1:1+0.5% triethylamine) to afford 5-chloro-1′-[trans-3-(4-chlorophenyl)allyl]-3′-methyl-spiro[indoline-3,4′-piperidine] (1.63 g). 1H NMR (600 MHz, CDCl3) 0.69 (d, J=9 Hz, 3H), 1.89 (m, 2H), 2.0 (m, 3H), 2.86 (dd, 1H), 2.95 (m, 1H), 3.17 (d, J=7.2 Hz, 2H), 3.31 (d, J=12 Hz, 1H), 3.58 (d, J=12 Hz, 1H), 3.65 (m, 1H), 6.30 (dt, J=7.2, 18.0 Hz, 1H), 6.49 (d, J=8.0 Hz, 1H), 6.50 (d, J=7.0 Hz, 1H), 2H), 6.94 (d, J=0.9 Hz, 1H), 6.97 (dd, J=7.0, 0.9 Hz, 1H), 7.25-7.33 (m, 4H); MS (ES+) 387/389 (M+H+).

Workup

  1. temperatureheated
  2. temperatureat reflux under argon for 12 hours
  3. temperaturethe solution refluxed for 2 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. washwashed with brine
  6. dry with materialdried (sodium sulphate)
  7. concentrationconcentrated
  8. customThe dark residue was purified by silica gel chromatography (cyclohexane:ethyl acetate 1:1+0.5% triethylamine)

Sources & evidence

ORD record
ord-6f50f24f712044b782409f0875ea2e45
Source dataset
uspto-grants-2012_11
Patent number
US08309567B2

Reaction notes

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