Reaktion #975417

Reaktionsgleichung

(2S)-2-[(4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid

diisopropyl (R)-(+)-malate

1-(5-phenyl-[1,2,4]oxadiazol-3-yl)piperazine

(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2S)-2-methyl-4-(4-methylpyridin-2-yl)piperazin-1-yl]carbonyl}hexanamide

Intermediate 11

(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2S)-2-methyl-4-(4-methylpyridin-2-yl)piperazin-1-yl]carbonyl}hexanamide

DIEA

DIEA

1-hydroxy-7-azabenzotriazole

fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate

→

title compound

Ausbeute 42.0%

(5R)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(5-phenyl-1,2,4-oxadiazol-3-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one

Ausbeute 42.0%

Lösungsmittel

DCM

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooled at 0° C
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 5 hours at RT
3. 3
   SonstigePurification

Vorschrift

To a cold solution (−15° C.) of (2S)-2-[(4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid (150 mg, 0.65 mmol, prepared according to WO 94/02447 or similarly to Seebach et al., 1990, Org. Syntheses, Coll. Vol. III, p 153-159 but starting from diisopropyl (R)-(+)-malate) in anhydrous DCM (1.8 mL) were added DIEA (115 μL, 0.69 mmol), 1-hydroxy-7-azabenzotriazole (89 mg, 0.65 mmol, Fluka) and fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (206 mg, 0.78 mmol, Aldrich). The reaction mixture was stirred at −15° C. for 15 min and at RT for 1 h, then cooled at 0° C. A solution of 1-(5-phenyl-[1,2,4]oxadiazol-3-yl)piperazine (230 mg, 0.78 mmol, Intermediate 11 parent form) and DIEA (115 μL, 0.69 mmol) in anhydrous DCM (1 mL) was added. The reaction mixture was stirred for 5 hours at RT and then poured on a silica column (wet with c-Hex/EtOAc 4:1). Purification was performed with a gradient cHex/EtOAc 4:1 to c-Hex/EtOAc 3:1 to give 120 mg (42%) of the title compound as a white powder. HPLC, Rt: 4.5 min (purity: 100%). LC/MS, M+(ESI): 443.3.

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