Cesium carbonate → Ethyl 8-[(3,5-difluoropyridine-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 1844185Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1844185
Cl[CH2:2][C:3]1[C:8]([F:9])=[CH:7][N:6]=[CH:5][C:4]=1[F:10].C(=O)([O-])[O-].[Cs+].[Cs+].[OH:17][C:18]1[C:19]2[N:20]([C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:25]([CH3:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1>CN(C=O)C.O>[F:10][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([F:9])[C:3]=1[CH2:2][O:17][C:18]1[C:19]2[N:20]([C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:25]([CH3:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 21717316Ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylateHCID 867182084-(Chloromethyl)-3,5-difluoropyridine

Produkt 1

HCID 86718212Ethyl 8-[(3,5-difluoropyridine-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

At RT, 1.86 g of 4-(chloromethyl)-3,5-difluoropyridine (Example 115A, 9.1 mmol, 2.0 equivalent) and 4.44 g of caesium carbonate (13.6 mmol, 3 equivalent) were added to 1.0 g of ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 3A, 4.54 mmol, 1.0 equivalent) in 100 ml of DMF, and the mixture was stirred at 60° C. for 1 h. The mixture was then diluted with 500 ml of water and extracted twice with in each case 300 ml of ethyl acetate. The combined organic phases were washed with 400 ml of saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated using a rotary evaporator. The residue obtained was purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 7:1 to 1:1). This gave 900 mg (54% of theory) and 200 mg (13% of theory; purity about 85%) of the title compound.

Aufarbeitung

  1. extractionextracted twice with in each case 300 ml of ethyl acetate
  2. washThe combined organic phases were washed with 400 ml of saturated aqueous sodium chloride solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customa rotary evaporator
  6. customThe residue obtained
  7. customwas purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 7:1 to 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-01ae87594b5c40dcb2b0eac28b45d450
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946215B2

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