Toluene → 6-[4-(2-Methoxy-vinyl)-2-methyl-phenoxy]-nicotinonitrile

Temperature

0 °C

Suspend (methoxymethyl)triphenylphosphonium chloride (1.14 g, 3.34 mmol) in THF (11 mL) under N2 and cool the mixture at 0° C., add slowly 0.5M KHMDS in toluene (6.7 mL, 3.34 mmol) and stir at 0° C. for 30 min. Cool the mixture at −78° C. and add a solution of aldehyde from step 1 above (663 mg, 2.78 mmol) in THF (2 mL). Warm the mixture slowly to room temperatures and stir for 1 h. Add water and extract the aqueous layer with Et2O. Dry the organic layer over MgSO4. Eliminate the solvent and purify by flash chromatography on silica gel (eluent: gradient from EtOAc/hexane 10/90 to 20/80) to get the title compound (530 mg, 76%). Electrospray MS M+1 ion=267. 1H-NMR (CDCl3, 300 MHz, mixture of isomers): 8.47-8.45 (m, 2H), 7.92-7.86 (m, 2H), 7.50-7.45 (m, 1H), 7.15-6.93 (m, 5H), 6.14 (d, 1H, J=7.1 Hz), 5.79 (d, 1H, J=13.2 Hz), 5.20 (d, 1H, J=7.1 Hz), 3.78 (s, 3H), 3.68 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H).

1. temperatureCool the mixture at −78° C.
2. temperatureWarm the mixture slowly to room temperatures
3. stirringstir for 1 h
4. extractionAdd water and extract the aqueous layer with Et2O
5. dry with materialDry the organic layer over MgSO4
6. custompurify by flash chromatography on silica gel (eluent: gradient from EtOAc/hexane 10/90 to 20/80)

ORD record

ord-5706938121b240cb878f42c75a61df02

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07531557B2