Reaction #44605

Reaction equation

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

Solvents

DMF

EDC

DMF

water

ethyl acetate

ethyl acetate

Conditions

Workup

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

Procedure

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:

Source