Potassium Carbonate → HCID 86674670, Verbindung

HRID 1500600Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1500600
C(=O)([O-])[O-].[K+].[K+].Cl[CH2:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[CH:12]=[O:13].[OH:19][C:20]1[C:25]([CH3:26])=[CH:24][C:23]([NH:27][C:28](=[O:30])[CH3:29])=[CH:22][C:21]=1[CH3:31]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C>[CH:12]([C:11]1[CH:14]=[CH:15][C:16]([O:17][CH3:18])=[C:9]([CH:10]=1)[CH2:8][O:19][C:20]1[C:25]([CH3:26])=[CH:24][C:23]([NH:27][C:28](=[O:30])[CH3:29])=[CH:22][C:21]=1[CH3:31])=[O:13]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 89896N-(4-Hydroxy-3,5-dimethylphenyl)acetamideHCID 104237Benzaldehyde, 3-(chloromethyl)-4-methoxy-

Produkt 1

HCID 86674670HCID 86674670, VerbindungAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A suspension of 2,6-dimethyl-4-nitrophenol (4a, 1.58 g, 9.45 mmol) in AcOH (20 ml), MeOH (15 ml), and THF (10 ml) in a hydrogenator vessel was treated with acetic anhydride (6 ml, 63.6 mmol) and PtO2 (200 mg, 0.881 mmol), pressurized to 50 p.s.i. with H2 and shaken for 24 h. The reaction mixture was returned to atmospheric pressure, diluted with EtOAc, washed with H2O, dried (MgSO4), filtered and concentrated under reduced pressure. N-(4-hydroxy-3,5-dimethylphenyl)acetamide (4b) was isolated as a white solid that was pure based upon LCMS analysis and used without further purification. Potassium carbonate (810 mg, 5.34 mmol) was added to a solution of tetrabutylammonium iodide (78.9 mg, 0.534 mmol), 3-(chloromethyl)-4-methoxybenzaldehyde (5a, 197 mg, 1.07 mmol), and N-(4-hydroxy-3,5-dimethylphenyl)acetamide (4b, 211 mg, 1.18 mmol) in 20 ml of acetonitrile. The reaction mixture was heated to 150° C. in the microwave for 1 h, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with 5-50% EtOAc/DCM gradient to afford the desired product 6a (196 mg, 56%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.15 (s, 3 H), 2.28 (s, 6 H), 3.93 (s, 3 H), 4.83 (s, 2 H), 7.02 (d, J=8.4 Hz, 1H), 7.13 (s, 1 H), 7.17 (s, 2 H), 7.89 (dd, J=8.4, 2.0 Hz, 1 H), 8.12 (d, J=1.8 Hz, 1H), 9.94 (s, 1 H); LCMS: (electrospray+ve), m/z 328.2 (MH)+, tR=3.16 min, UV254=>95%. N-(4-(5-formyl-2-methoxybenzyloxy)-3,5-dimethylphenyl)acetamide (6a, 145 mg, 0.441 mmol), 2-amino-N-(furan-2-ylmethyl)benzamide (3b, 105 mg, 0.486 mmol), and 0.2 equiv of Yb(OTf)3 in 5 ml of EtOH were heated at 80° C. for 4 h. The reaction mixture was concentrated under reduced pressure and the residue was chromatographed on silica-gel using 7-60% ethyl acetate in hexanes to give the desired product 7a (40.9 mg, 0.078 mmol, 17.6% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.15 (s, 3 H), 2.21 (s, 6 H), 3.77 (d, J=15.7 Hz, 1 H), 3.84 (s, 3 H), 4.41 (s, 1 H), 4.70-4.87 (m, 2 H), 5.35 (d, J=15.7 Hz, 1 H), 5.78 (s, 1 H), 6.20 (d, J=2.9 Hz, 1 H), 6.24-6.32 (m, 1 H), 6.53 (d, J=8.0 Hz, 1 H), 6.76-6.91 (m, 2 H), 7.03 (br. s., 1 H), 7.13 (s, 2 H), 7.30-7.37 (m, 2 H), 7.49 (d, J=2.0 Hz, 1 H), 7.92-8.03 (m, 1 H); LC/MS (electrospray+ve), m/z 526.2 (MH)+, Retention time t=5.71 min; Purity: UV220>98%, UV254>98%; HRMS (ESI): m/z calcd for C31H31N3O5 [M+H]+526.2351, found 526.2350.

Aufarbeitung

  1. customused without further purification
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography on silica gel with 5-50% EtOAc/DCM gradient

Quellen und Nachweise

ORD-Eintrag
ord-a8bbefe5379d4165b7ddcbc722fbcfb3
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206154B2

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