反应详情

A mixture of 26 mg (0.07 mmol) of 1-(t-butoxycarbonyl)-4-(3-iodo-2,2-dimethylpropyl)piperidine (from EXAMPLE 98, Step H) and 2 mg (0.007 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]nickel (II) chloride in ether (5 mL) at reflux was treated with phenylmagnesium bromide (0.13 mL of 3.0 M solution in ether). The resulting mixture was heated at reflux for 12 h, cooled and quenched with H2O and sat'd NaCl. The mixture was extracted 3× with CH2Cl2 and the combined organic layers were dried over Na2SO4, filtered and the filtrate concentrated. The residue was purified by column chomatography on 10 g of silica using a gradient of 0-5% MeOH/CH2Cl2 (v/v), then 10% MeOH/CH2Cl2+2% NH401H (v/v), to give 9 mg (56%) of the title compound: 1H NMR (500 MHz) δ 0.89 (s, 6H), 1.18-1.27 (4H), 1.52-1.59 (m, 1H), 1.71 (d, J=12.3,21).2.46 (bs, 1H) 2.52 (s, 2H), 2.65 (t, J=11.9, 2H). 3.06 (d,J=12.2, 2H), 7.13 (d, J=7.3, 2H), 7.22 (t, J=7.1, 11H), 7.28 (t, J=6.7, 2H).

1. temperatureat reflux
2. temperatureThe resulting mixture was heated
3. temperatureat reflux for 12 h
4. temperaturecooled
5. customquenched with H2O
6. extractionThe mixture was extracted 3× with CH2Cl2
7. dry with materialthe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationthe filtrate concentrated
10. customThe residue was purified by column chomatography on 10 g of silica using a gradient of 0-5% MeOH/CH2Cl2 (v/v)