Potassium Carbonate → 4-[(E)-2-(2,6-dichloro-4-morpholin-4-yl-phenyl)-vinyl]-3-nitrobenzoic acid methyl ester

Temperatur

95 °C

A mixture of 4-bromomethyl-3-nitrobenzoic acid methyl ester (1.01 g, 3.68 mmol) (from Example 3-8) and triphenylphosphine (1.06 g, 4.05 mmol) in DMF (20 mL) under N2 was heated at 95° C. Upon disappearance of the starting ester by TLC, 2,6-dichloro-4-morpholin-4-yl-benzaldehyde (1.15 g, 4.42 mmol) was added followed by K2CO3 (1.02 g, 7.36 mmol). The mixture was heated at 95° C. for 22.5 h then was allowed to cool to ambient temperature. The mixture was partitioned between EtOAc/DCM (700 mL) and Water (200 mL). The resulting orange precipitate was filtered and the organic phase was dried over Na2SO4 and concentrate under reduced pressure. The residue was triturated with EtOAc/Et2O to yield additional orange solid. The combined orange solids provided 4-[(E)-2-(2,6-dichloro-4-morpholin-4-yl-phenyl)-vinyl]-3-nitrobenzoic acid methyl ester. 1H NMR (400 MHz, DMSO-d6): δ 8.46 (d, J=1.77 Hz, 1H), 8.24 (dd, J=8.27, 1.71 Hz, 1H), 8.11 (d, J=8.21 Hz, 1H), 7.49 (d, J=16.42 Hz, 1H), 7.33 (d, J=16.42 Hz, 1H), 7.10 (s, 2H), 3.91 (s, 3H), 3.67-3.73 (m, 4H), 3.22-3.27 (m, 4H). MS (m/z) 437.1 (M+1).

1. temperatureThe mixture was heated at 95° C. for 22.5 h
2. temperatureto cool to ambient temperature
3. customThe mixture was partitioned between EtOAc/DCM (700 mL) and Water (200 mL)
4. filtrationThe resulting orange precipitate was filtered
5. dry with materialthe organic phase was dried over Na2SO4
6. concentrationconcentrate under reduced pressure
7. customThe residue was triturated with EtOAc/Et2O
8. customto yield additional orange solid

ORD-Eintrag

ord-26a03d7d688e4e46b1bfc91a34c2b7cb

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08222248B2