Ethanol → Ethyl 3-[2-fluoro-4-[[3-methoxy-4-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)phenyl]methoxy]phenyl]propanoate

To a solution of spiro[indene-1,4′-piperidine] (0.515 g, 2.58 mmol) in EtOH (15 mL) is added N,N-diisopropylethylamine (1.4 mL, 2.589 mmol) and 3-[4-(4-bromomethyl-2-trifluoromethyl-benzyloxy)-2-fluoro-phenyl]-propionic acid ethyl ester (1.1 g, 2.58 mmol) at room temperature and the reaction mixture is stirred for 16 hours at 80° C. The mixture is concentrated, diluted with water, and extracted with EtOAc (2×50 mL). The combined extracts are washed with water (20 mL) and saturated brine (20 mL), dried over Na2SO4, filtered, and concentrated. The crude material is purified by silica gel column chromatography to give the title compound as a colorless gel (0.650 g, 47.7%). 1H NMR (400 MHz, CDCl3) δ 7.42-7.35 (m, 2H), 7.31-7.29 (d, J=8 Hz, 1H), 7.20-7.01 (m, 3H), 7.05 (s, 1H), 7.01-6.99 (d, J=8 Hz, 1H), 6.64-6.93 (d, J=4 Hz, 1H), 6.86-6.83 (d, J=12 Hz, 1H) 6.77 (s, 1H), 5.05 (s, 2H), 4.03-3.98 (m, 2H), 3.79 (s, 3H), 3.57 (s, 2H), 2.89-2.86 (d, J=12 Hz, 2H), 2.79-2.76 (t, J=8 Hz, 2H), 2.55-2.53 (d, J=8 Hz, 2H), 2.41-2.35 (t, J=12 Hz, 2H), 2.10-2.05 (t, J=8 Hz, 2H), 1.22-1.17 (t, J=8 Hz, 3H).

1. concentrationThe mixture is concentrated
2. additiondiluted with water
3. extractionextracted with EtOAc (2×50 mL)
4. washThe combined extracts are washed with water (20 mL) and saturated brine (20 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material is purified by silica gel column chromatography

ORD 기록

ord-af27012965a9453d8c17b126f75a5a9b

출처 데이터셋

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08383642B2