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

HRID 1875549노트

반응식

HRID 1875549 반응식
[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

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 6212Chloroform용매HCID 6344Dichloromethane용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-6f50f24f712044b782409f0875ea2e45
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309567B2

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