Compound 4b

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InChIKey LOLLYFNYNFOTPB-UHFFFAOYSA-N

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a flame-dried, 50-mL, single-necked, Schlenk flask fitted with a magnetic stir bar, argon inlet and septum was added 1.40 g of KHMDS (7.0 mmol, 1.2 equiv) and 7.0 mL of anhydrous THF (1.0 M in KHMDS). The solution was stirred at rt until a homogeneous solution resulted and then was cooled to -78 °C (internal) with a dry ice/acetone bath. The reaction mixture was stirred at -78 °C for 5 min and then a solution of 0.75 g tert-butoxy nitrile 3b (5.86 mmol) and 1.4 mL (5.03 mmol, 1.1 equiv) TIPSCl in 7.9 mL of anhydrous THF (∼0.5 M solution in nitrile) was added dropwise via cannula over 10 min. The resulting bright-yellow reaction mixture was stirred for 2 h at -78 °C and then was allowed to warm to 0 °C and was stirred for 5 min during which time the color changed from yellow to orange. The reaction mixture was concentrated under high vaccum (0.5 mm Hg) and the resulting thick, orange gel (ca. 3 mL) was taken up in 20 mL of anhydrous hexanes (20 mL) and was stirred vigorously under argon. The heterogeneous solution was opened to air and filtered through a pad of packed Celite (ca. 5 g) using a 30-mL, glass-sintered Buchner funnel and then was collected into a flame-dried, weighed 50-mL, round-bottomed flask. The filter cake and Schlenk flask were further washed with 15 mL of anhydrous hexanes. The clear, orange filtrate was concentrated under vacuum (0.5 mm Hg) and then was stirred under high vacuum (0.2 mm Hg) for 12 h at ambient temperature to afford 1.56 g (94%) of 4b as an orange liquid, which was used in subsequent reactions without further purification. ¹H NMR: (500 MHz, CDCl₃) 1.96 (s, 3 H, H₃C(3)), 1.26 (s, 9 H, H₃C(5)), 1.12 – 1.05 (m, 21 H, HC(6) and H₃C(7)); ¹³C NMR: (125 MHz, C₆D₆) 209.3 (C(1)), 86.3 (C(2)), 78.9 (C(4)), 28.8 (C(3)), 18.3 (C(6)), 18.0 (C(5)), 12.0 (C(7)).; IR: (NaCl plates, neat) 2945 (s), 2868 (s), 2037 (s), 1464 (s), 1384 (m), 1357 (m), 1257 (w), 1166 (s), 1071 (w), 996 (m), 919 (w), 883 (s), 815 (w), 732 (m), 671 (s); MS: (70 eV, EI) 283.2 (5.4), 184.1 (47.0), 158.1 (13.9), 157.1 (100.0), 115.1 (53.4), 87.1 (27.6), 73.0 (28.7), 59.0 (41.4), 57.0 (30.6); HRMS: calcd for C₁₆H₃₃ONSi: 283.2332, found: 283.2330.