2-(4-formylphenyl)-2-methylpropanenitrile

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

Procedure: A mixture of Example 35B (2.24 g, 12.9 mmol), 1-(1-isocyanoethylsulfonyl)-4-methylbenzene (2.71 g, 12.9 mmol), and K2CO3 (2.15 g, 15.5 mmol) in MeOH (60 mL) was heated at reflux for 2 hr. The reaction was cooled to ambient temperature, and the volatiles removed at reduced pressure. The residue was partitioned between H2O and Et2O. The separated aqueous phase was extracted with Et2O, and the combined organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Flash chromatography (Analogix® Intelliflash 280™; 15% to 40% EtOAc/hexanes eluant; SF40-150 g column) yielded 2.35 g (80%) of the title compound as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.71-7.61 (m, 4H), 2.37 (s, 3H), 1.71 (s, 6H). MS (DCI+) m/z 227 (M+H). at reflux for 2 hr the volatiles removed at reduced pressure The residue was partitioned between H2O and Et2O The separated aqueous phase was extracted with Et2O the combined organic layer was washed with brine dried (Na2SO4) filtered concentrated in vacuo

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

Procedure: A suspension of lithium tris(dihexylamino)aluminum hydride, prepared according to Cha, J. S., et al; Org. Prep. Proc. Int. 1992, 24(3), 331-334, (21.2 g, 36 mmol) in THF (20 mL) was added via syringe to a solution of Example 35A (3.50 g, 20.6 mmol) in THF (50 mL) at 0° C. The reaction was allowed to proceed for 8 hr at 0° C., and then carefully quenched by addition of 3 N aq HCl(100 mL). The mixture was diluted with EtOAc, and the separated aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine causing a white precipitate to form, which was filtered off. The filtrate was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting yellow solid was triturated with hexanes and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography (Analogix® Intelliflash 280; 5% to 25% EtOAc/hexanes eluant; SF40-115 g column) to yield 2.24 g (63%) of the title compound as a pale yellow oil. 1H NMR (300 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.00-7.93 (m, 2H), 7.80-7.74 (m, 2H), 1.73 (s, 6H). MS (DCI+) m/z 173 (M+). prepared carefully quenched by addition of 3 N aq HCl(100 mL) The mixture was diluted with EtOAc the separated aqueous phase was extracted with EtOAc The combined organic layer was washed with brine causing a white precipitate to form which was filtered off The filtrate was dried over Na2SO4 filtered concentrated in vacuo The resulting yellow solid was triturated with hexanes filtered The filtrate was concentrated in vacuo the residue was purified by flash chromatography (Analogix® Intelliflash 280