Diisopropylethylamine → (S)-1-{4-[Bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-4-methyl-2-morpholin-4-yl-pentan-1-one

온도

0 °C

4-Methyl-2-morpholin-4-yl-pentanoic acid (0.200 g, 0.994 mmol, Example 23, Step A) was dissolved in dry DMF (4 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.346 mL, 1.99 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.379 g, 0.994 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.287 g, 0.994 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 20 minutes at ambient temperature, reaction mixture was mixed with 50 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was further purified by flash chromatography (40% EtOAc in hexane) to provide 0.284 g (60%) of the pure titled compound as a white foam; mp 55-63° C. APCI-MS m/z 472.3.0 (MH+).

1. customThe resulting reaction mixture
2. stirringAfter stirring for, sequentially, 10 minutes at 0° C.
3. custom20 minutes at ambient temperature, reaction mixture
4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL)
5. dry with materialwas dried over Na2SO4
6. concentrationThe solution was concentrated in vacuo
7. customaffording a viscous oil
8. customThe crude product was further purified by flash chromatography (40% EtOAc in hexane)

ORD 기록

ord-3c5787205eaf43f1bcaa63ecc752b545

출처 데이터셋

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06458781B1