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

HRID 1875549ノート

反応式

HRID 1875549 の反応式
[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

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6344Dichloromethane溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-6f50f24f712044b782409f0875ea2e45
出典データセット
uspto-grants-2012_11
特許番号
US08309567B2

反応ノート

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