tert-Butyl 4-oxopiperidine-1-carboxylate → tert-butyl 4-(6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

To a colorless solution of 6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (500 mg, 1.63 mmol) in THF (16 mL) was dropwise added sec-BuLi at −78° C. under N2 over 6 min, and the resulting tan solution was stirred for 2 hr. Tert-butyl 4-oxopiperidine-1-carboxylate (1.13 g, 5.70 mmol) in THF (3 mL) was dropwise added over 10 min to give a light tan solution at −78° C. under N2, and continued stirring for 2 hr. The reaction was quenched with sat. NH4Cl (30 mL), extracted with Et2O (2×50 mL). The combined organic phase was washed with brine (30 mL), dried (MgSO4), concentrated on rotary vacuo and purified on Biotage Flash Collector eluting with 20˜50% EtOAc/Hexanes (800 mL) to give the expected product, tert-butyl 4-(6-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidine-1-carboxylate (400 mg, 48%), as a light yellow solid. 1H-NMR (400 MHz, CHLOROFORM-D) δ ppm 1.25 (t, J=7.68 Hz, 18 H) 1.64 (s, 9 H) 1.94 (dt, J=15.17, 7.65 Hz, 5 H) 2.33-2.44 (m, 2 H) 3.42 (s, 2 H) 4.24 (d, J=7.05 Hz, 2 H) 6.88 (d, J=3.53 Hz, 1 H) 7.38-7.41 (m, 3 H); Mass spec. 508.25 (MH+) calc. for C26H42ClN3O3Si 507.27.

Provenance & Evidence