Diethyl Ether → HCID 86758553, compound

Temperature

0 °C

(S)-4-Methyl-2-[methyl-(3-methyl-butyl)-amino]-pentanoic acid (0.300 g, 1.39 mmol) 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 (0.728 mL, 4.18 mmol) and solid O-benzotriazol-1-yl-N,N,N″,N′-tetramethyluronium hexafluorophosphate (0.528 g, 1.39 mmol). The resulting reaction mixture was stirred at that temperature for 25 minutes; solid 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.415 g, 1.39 mmol) was then added. After stirring for, sequentially, 20 minutes at 0° C. and 60 minutes at ambient temperature, reaction mixture was mixed with 60 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 an viscous oil. The crude product was further purified by flash chromatography (40% EtOAc in hexane) and treated with ethereal HCl. Subsequent concentration in vacuo and drying under vacuum provided 0.460 g (65%) of the pure titled compound as a white foam: mp 37-46° C. APCI-MS m/z 459.4 (MH+).

1. customThe resulting reaction mixture
2. stirringAfter stirring for, sequentially, 20 minutes at 0° C.
3. custom60 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 an viscous oil
8. customThe crude product was further purified by flash chromatography (40% EtOAc in hexane)
9. additiontreated with ethereal HCl
10. concentrationSubsequent concentration in vacuo
11. customdrying under vacuum

ORD record

ord-cbc07d55ba04496c826c479440ae727a

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06458781B1