1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (1-Biphenyl-4-yl-ethyl)-{2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

DIPEA (182 mg, 0.24 mL, 1.4 mmol) was added to a stirred solution of [(1-biphenyl-4-yl-ethyl)-tert-butoxycarbonyl-amino]-acetic acid (100 mg, 0.28 mmol) in DMF (5 mL). HOBT (42 mg, 0.31 mmol) and EDCI (135 mg, 0.7 mmol) were then added at room temperature. After 2 minutes, (5-Fluoro-2-trifluoromethyl-phenyl)-piperazin-1-yl-methanone hydrochloride salt (105 mg, 0.3 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (using 60-120 silica gel and 30-50% EtOAc in hexane as eluent) to afford 43 mg (27.56% yield) of (1-biphenyl-4-yl-ethyl)-{2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester, LCMS Purity: 96.02%. 1H NMR (CDCl3): δ 7.78 (t 1H), 7.64-7.5 (s, 4H), 7.5-7.3 (m, 5H), 7.24 (d, 1H), 7.04 (m, 1H), 5.8-5.2 (bd, 2H), 4.0 (s, 1H), 3.8 (s, 3H), 3.6-3.2 (m, 5H), 3.1 (s, 3H), 1.5 (s, 9H).

1. extractionthe product was extracted with EtOAc
2. washthe organic layer was washed with brine
3. dry with materialThe organic phase was dried over Na2SO4
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified by column chromatography (using 60-120 silica gel and 30-50% EtOAc in hexane as eluent)

ORD-Eintrag

ord-e3a174d798884e94a4be25a49e87e325

Quelldatensatz

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07842696B2