Diisopropylamine → tert-butyl 4-(1H-imidazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1725768

Reaktionsgleichung

Reaktionsgleichung von HRID 1725768
O[C:2]1([C:15]2[NH:16][CH:17]=[CH:18][N:19]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(NC(C)C)(C)C.CS(Cl)(=O)=O>CN(C=O)C.O.[OH-].[Na+]>[NH:16]1[CH:17]=[CH:18][N:19]=[C:15]1[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]=1

Komponenten

7

Edukt 3

HCID 7912Diisopropylamine2×HCID 31297Methanesulfonyl chloride2×HCID 23084083tert-butyl 4-hydroxy-4-(1H-imidazol-2-yl)piperidine-1-carboxylate

Produkt 1

HCID 69053296tert-butyl 4-(1H-imidazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylateAusbeute 76,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl 4-hydroxy-4-(1H-imidazol-2-yl)piperidine-1-carboxylate (10.5 g) and diisopropylamine (13.8 mL, 2.5 equiv.) in anhydrous DMF under N2 at 0° C. was added in one portion of methanesulfonyl chloride (6.19 mL, 2 equiv.). The reaction was stirred at 0° C. for 2 hours when a further 2 equivalents of methanesulfonyl chloride and 2.5 equivalents of diisopropylamine was added and the resulting mixture stirred at room temperature overnight. The mixture was diluted with water (200 mL) and adjusted pH 9 with 1 N NaOH and then extracted with ethyl acetate (3×). The combined ethyl acetate layers was dried over MgSO4, filtered and evaporated. The residue was purified by column chromatography on silica eluting with 5% methanol in dichloromethane with 0.5% ammonium hydroxide to give tert-butyl 4-(1H-imidazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (7.5 g).

Aufarbeitung

  1. additionwas added
  2. extractionextracted with ethyl acetate (3×)
  3. dry with materialThe combined ethyl acetate layers was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica eluting with 5% methanol in dichloromethane with 0.5% ammonium hydroxide

Quellen und Nachweise

ORD-Eintrag
ord-e19b86e03737427193fd8c369ce3d3b2
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07491737B2

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