Ethyl Acetate → 1-[6-(4-Hydroxy-3,5-dimethyl-phenyl)-3-methoxy-pyridazin-4-yl]-propan-1-one

HRID 2426523Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2426523
Cl[C:2]1[N:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]([C:10](=[O:13])[CH2:11][CH3:12])[CH:3]=1.[CH3:14][C:15]1[CH:20]=[C:19](B2OC(C)(C)C(C)(C)O2)[CH:18]=[C:17]([CH3:30])[C:16]=1[OH:31].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[OH:31][C:16]1[C:17]([CH3:30])=[CH:18][C:19]([C:2]2[N:7]=[N:6][C:5]([O:8][CH3:9])=[C:4]([C:10](=[O:13])[CH2:11][CH3:12])[CH:3]=2)=[CH:20][C:15]=1[CH3:14]

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27346492,6-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 230924891-(6-Chloro-3-methoxy-pyridazin-4-yl)-propan-1-one

Produkt 1

HCID 1363396351-[6-(4-Hydroxy-3,5-dimethyl-phenyl)-3-methoxy-pyridazin-4-yl]-propan-1-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

2 g of 1-(6-Chloro-3-methoxy-pyridazin-4-yl)-propan-1-one and 1.73 g of tetrakis(triphenylphosphine) palladium (0) are dissolved in 10 ml DME and the solution is stirred for 5 min at RT under argon. 3 g of 2,6-Dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol and 10 ml of a 2M aqueous solution of sodium carbonate are added and the reaction solution is stirred at 95° C. for 4 h. The reaction solution is poured into ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic phase is dried (MgSO4), filtered and evaporated under reduced pressure. The product is purified by silica gel chromatography, eluting with a gradient of ethyl acetate in heptane, followed by purification by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). Yield 1.69 g. LC-MS (ES+) 287 (M+H)+.

Aufarbeitung

  1. stirringthe reaction solution is stirred at 95° C. for 4 h
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialThe organic phase is dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe product is purified by silica gel chromatography
  7. washeluting with a gradient of ethyl acetate in heptane
  8. customfollowed by purification by preparative RP-HPLC
  9. washeluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-6499fe91739946ebb6af6fbc6ae8a9c2
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07968546B2

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