ethyl 2-cyano-3,3-dimethyl-4-phenylbutanoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated H2SO4 (2.35 mL, 44.0 mmol) was added dropwise to ethyl 2-cyano-3,3-dimethyl-4-phenylbutanoate (1.08 g, 4.4 mmol) at 0° C. to give an orange solution. The reaction was allowed to warm to room temperature and was stirred for 24 h. Ice water (10 mL) was added to the deep red reaction to give an opaque yellow mixture. The reaction was basified with NH4OH (20 mL) and extracted with ether (3×10 mL). The organic extracts were washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to give bright yellow oil. Purified by flash column chromatography (20% ethyl acetate in hexanes, Rf=0.30) afforded the title compound as bright yellow crystalline solid (392.4 mg, 36.4% yield). 1H NMR (500 MHz, CDCl3) δ 7.39 (d, J=7.5 Hz, 1H), 7.31-7.28 (m, 2H), 7.18 (d, J=7.2 Hz, 1H), 6.33 (s, 2H), 4.26 (q, J=7.1 Hz, 2H), 2.65 (s, 2H), 1.34 (t, J=7.1 Hz, 3H), 1.20 (s, 6H). to give an orange solution to give an opaque yellow mixture extracted with ether (3×10 mL) The organic extracts were washed with water and brine dried over Na2SO4 concentrated under reduced pressure to give bright yellow oil Purified by flash column chromatography (20% ethyl acetate in hexanes, Rf=0.30)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-cyano-3-methylbut-2-enoate (0.91 mL, 6 mmol) in ether (4 mL) under N2 was added 1.0 M benzylmagnesium chloride in ether (9 mL, 9 mmol) dropwise to give a pale yellow solution. The reaction was stirred at room temperature for 3 h, and was then cooled to 0° C. and acidified with 10% HCl (10 mL). The organic layer was isolated, washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to give bright yellow oil. Purification by flash column chromatography (10% ethyl acetate in hexanes, Rf=0.26) gave the title compound as a pale yellow oil (1.08 g, 73.5%). 1H NMR (500 MHz, CDCl3) δ 8.02 (d, J=7.6 Hz, 1H), 7.51 (t, J=7.6 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.22 (d, J=7.6 Hz, 2H), 4.22 (m, 2H), 3.44 (s, 1H), 3.07 (d, J=16.5 Hz, 1H), 2.83 (d, J=16.5 Hz, 1H), 1.28 (t, J=7.1 Hz, 2H), 1.18 (s, 3H), 1.15 (s, 3H). to give a pale yellow solution was then cooled to 0° C. The organic layer was isolated washed with water and brine dried over Na2SO4 concentrated under reduced pressure to give bright yellow oil Purification by flash column chromatography (10% ethyl acetate in hexanes, Rf=0.26)

Conditions: temp:0.00; pressure:0.00; stir: