Reaktion #44605

Reaktionsgleichung

IPEA

HOBT

(E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid trifluoroacetate

(1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochloride

sodium hydride

sodium hydrogencarbonate

→

title compound

1-[(1R,2R)-2-hydroxy-1-(3,4,5-trifluorophenyl)propyl]-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}piperidin-2-one

Lösungsmittel

DMF

EDC

DMF

water

ethyl acetate

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe organic layer was separated
2. 2
   Trocknendried over magnesium sulfate
3. 3
   Einengenconcentrated under reduced pressure
4. 4
   Filtrationcollected by filtration
5. 5
   Sonstigeto give 3.16 g of a condensed substance
6. 6
   SonstigeThe resulting reaction solution
7. 7
   workup.STIRRINGwas stirred at room temperature for 15 min
8. 8
   SonstigeThe organic layer was separated
9. 9
   Trocknendried over magnesium sulfate
10. 10
    Einengenconcentrated under reduced pressure
11. 11
    SonstigeThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent: heptane to ethyl acetate)

Vorschrift

IPEA (4 mL), HOBT (1.11 g), and EDC (1.57 g) were added to a DMF solution (40 mL) of (E)-5-chloro-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]valeric acid trifluoroacetate (CAS Registry No. 870850-40-1, 3.69 g) and (1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochloride (1.98 g). This reaction solution was stirred at room temperature for 3.5 hr, and ethyl acetate and a saturated sodium hydrogencarbonate aqueous solution were added thereto. The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was suspended in diisopropyl ether and collected by filtration to give 3.16 g of a condensed substance. To a DMF solution (50 mL) of this condensed substance (3.16 g), sodium hydride (containing 40% mineral oil, 278 mg) was added at 0° C. The resulting reaction solution was stirred at room temperature for 15 min, and ethyl acetate and water were added thereto. The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent: heptane to ethyl acetate) to give 2.3 g of the title compound. The physical property values of this compound were as follows:

Quelle