2-(4-Chlorophenoxy)aniline → 1-Acetyl-N-(3-(1-(2-(4-chlorophenoxy)phenylamino)ethyl)phenyl)-N-ethylpiperidine-4-carboxamide

HRID 1043032

反応式

HRID 1043032 の反応式
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[NH2:9])=[CH:4][CH:3]=1.[C:16]([N:19]1[CH2:24][CH2:23][CH:22]([C:25]([N:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36](=O)[CH3:37])[CH:31]=2)[CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.[Cl-].C(O[Ti+](OC(C)C)OC(C)C)(C)C.O.CO>[C:16]([N:19]1[CH2:20][CH2:21][CH:22]([C:25]([N:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([CH:36]([NH:9][C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]3[CH:14]=[CH:15][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH3:37])[CH:31]=2)[CH2:28][CH3:29])=[O:26])[CH2:23][CH2:24]1)(=[O:18])[CH3:17]

参加物

9

反応物 4

HCID 760102-(4-Chlorophenoxy)anilineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 684308061-acetyl-N-(3-acetylphenyl)-N-ethylpiperidine-4-carboxamide

生成物 1

HCID 426136051-Acetyl-N-(3-(1-(2-(4-chlorophenoxy)phenylamino)ethyl)phenyl)-N-ethylpiperidine-4-carboxamide

試薬・触媒・溶媒 4

HCID 3084342Chlorotitanium triisopropoxide触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

2-(4-Chlorophenoxy)aniline (95 mg, 0.431 mmol, 1 eq) and 1-acetyl-N-(3-acetylphenyl)-N-ethylpiperidine-4-carboxamide (150 mg, 0.474 mmol, 1.1 eq) were stirred in dry dichloromethane (DCM) (2 mL) at room temperature for 10 min. Tri-isopropoxytitanium chloride (206 μL, 1.654 mmol, 2 eq) was added to the reaction mixture which was stirred at room temperature for 16 hours. Sodium triacetoxyborohydride (365 mg, 1.724 mmol, 4 eq) was then added to the reaction mixture and was stirred at room temperature for a further 24 h. The reaction mixture was then poured onto a solution of saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (120 mL). The organic layer was washed with brine (120 mL), dried over MgSO4, filtered and concentrated to give the crude as a yellow oil. Purification of the crude by flash chromatography (ISCO) eluting with a gradient [0-10% MeOH/DCM] gave as a pale yellow oil. 1H NMR (270 MHz, CDCl3) δ 0.98 (3H, dt, J=3.1, 7.0 Hz, CH3), 1.25 (1H, m, CH2), 1.50 (3H, d, J=6.2 Hz CH3), 1.50-1.71 (3H, m, CH2), 1.95 (3H, d, J=7.2 Hz) 2.05-2.20 (2H, m, CH2), 2.40 and 2.65 (1H, m, CH), 3.50-3.72 (3H, m, CH2), 4.30-4.61 (3H, m, CH and NH), 6.32 (1H, d, J=7.8 Hz, ArH), 6.55 (1H, q, J=7.3 Hz, Ar), 6.70-6.90 (4H, m, Ar), 6.95-7.05 (2H, m, Ar), 7.20-7.42 (4H, m, Ar); LCMS (90% MeOH and 10% H2O; Symmetry C18 reverse phase column) tr=2.38 min; (ES+), m/z 520.3; HRMS (ESI) calcd. for C30H35ClN3O3 (M+H)+ 520.2289, found 520.2343. HPLC 99.49% purity.

後処理

  1. stirringwas stirred at room temperature for a further 24 h
  2. extractionextracted with DCM (120 mL)
  3. washThe organic layer was washed with brine (120 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude as a yellow oil
  8. customPurification of the crude by flash chromatography (ISCO)
  9. washeluting with a gradient [0-10% MeOH/DCM]
  10. customgave as a pale yellow oil

出典と根拠

ORDレコード
ord-11d9dc68328847d4aedfebec0e68aef8
出典データセット
uspto-grants-2013_10
特許番号
US08558028B2

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