反应详情

A suspension of Ph3PCH3Br (53.4 mg, 0.15 mmol) in THF (500 μL) was cooled to 0° C. potassium bis(trimethylsilyl)amide (256 μL of a 0.5 M solution in toluene, 0.128 mmol) was added slowly and the reaction was kept at 0° C. After fifteen minutes, methyl[3-formyl-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (24.2 mg, 0.043 mmol) (Example 40) was dissolved in THF (1 mL) and was added via cannula to the reaction which was then slowly warmed to room temperature. After fifteen minutes at room temperature, the reaction was diluted with EtOAc (30 mL), and poured into NaHCO3 (10 mL). The organic extract was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 25% EtOAc/hexanes afforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)-5-vinylbenzyl]carbamate. Rf=0.42 (25% EtOAc/hexanes) LCMS=566.2 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.68 (broad singlet, 1H), 7.36 (s, 1H), 7.34 (d, J=8.0 Hz, 1H), 7.15 (broad singlet, 1H), 7.10 (d, J=10.5 Hz, 1H), 7.03 (d, J=8.0 Hz, 1H), 7.01 (dd, J=8.5, 2.0 Hz, 1H), 6.81 (d, J=2.0 Hz, 1H), 6.54 (d, J=8.5 Hz, 1H), 6.32-6.27 (m, 1H), 5.40 (d, J=18 Hz, 1H), 4.97 (d, J=11 Hz, 1H), 4.37 (broad singlet, 2H), 4.04 (broad singlet, 2H), 3.34 (s, 3H), 3.20 (s, 3H), 2.69 (m, 1H), 1.12 (d, J=7.0 Hz, 6H).

1. additionwas added slowly
2. customwas kept at 0° C
3. waitAfter fifteen minutes
4. additionwas added via cannula to the reaction which
5. waitAfter fifteen minutes at room temperature
6. extractionThe organic extract
7. washwas washed with brine (10 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by flash chromatography with 5% to 25% EtOAc/hexanes