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

HRID 1043033Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1043033
[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:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35](=O)[CH3:36])[CH:30]=2)[CH3:28])=[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[CH2:24][CH2:23][CH:22]([C:25]([N:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]([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)[CH3:36])[CH:30]=2)[CH3:28])=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17]

Komponenten

9

Edukt 4

HCID 760102-(4-Chlorophenoxy)anilineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 684278591-acetyl-N-(3-acetylphenyl)-N-methylpiperidine-4-carboxamide

Produkt 1

HCID 426136701-Acetyl-N-(3-(1-(2-(4-chlorophenoxy)phenylamino)ethyl)phenyl)-N-methylpiperidine-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3084342Chlorotitanium triisopropoxideKatalysatorHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

2-(4-Chlorophenoxy)aniline (118 mg, 0.541 mmol, 1 eq) and 1-acetyl-N-(3-acetylphenyl)-N-methylpiperidine-4-carboxamide (180 mg, 0.595 mmol, 1.1 eq) were stirred in dry dichloromethane (DCM) (2 mL) at room temperature for 10 min. Tri-isopropoxytitanium chloride (284 μL, 1.19 mmol, 2 eq) was added to the reaction mixture which was stirred at room temperature for 16 hours. Sodium triacetoxyborohydride (504 mg, 2.38 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 into 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 (167 mg, 61%) as a white foam. 1H NMR (270 MHz, CDCl3) δ 1.2-1.38 (2H, m, CH2), 1.50 (3H, d, J=6.1 Hz, CH3), 1.55-1.80 (2H, m, CH2), 1.90 (3H, d, J=6.7 Hz CH3), 2.10-2.30 (2H, m, CH2), 2.39 and 2.65 (1H, m, CH2), 3.15 (3H, s, NCH3), 3.69 and 3.49 (1H, d, J=13.4 Hz, CH), 4.25-4.60 (3H, m, NH and CH), 6.30 (1H, d, J=8.0 Hz, Ar) 6.55 (1H, q, J=7.0 Hz, ArH), 6.75-6.95 (4H, m, ArH), 7.00-7.15 (2H, m, ArH), 7.23-7.51 (4H, m, ArH); LCMS (90% MeOH and 10% H2O; Symmetry C18 reverse phase column) tr=2.15 min; (ES+), m/z 506.4 HRMS (ESI) calcd. for C29H32ClN3O3 (M+H)+ 505.2132, found 506.2193. HPLC 100% purity.

Aufarbeitung

  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 (167 mg, 61%) as a white foam

Quellen und Nachweise

ORD-Eintrag
ord-303c748deee34e6b816c61b92e21cd74
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08558028B2

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