tert-Butyl 4-oxopiperidine-1-carboxylate → 1-(tert-Butoxycarbonyl)-4-hydroxy-4-(2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)piperidine

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Reaction Conditions

Reaction Steps

To a solution of 3-bromo-2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (4.01 g, 17.6 mmol, from Step C) in THF (20 mL) was added tert-BuLi (1.7 M in pentane, 22.8 mL, 38.7 mmol) dropwise at −78° C. After stirring at −78° C. for 30 min., was added tert-butyl 4-oxo-1-piperidinecarboxylate (3.51 g, 17.6 mmol) in THF (10 mL) dropwise at −78° C. The mixture was stirred at −78° C. for 10 min. and at rt for 4 h. After the reaction was quenched with aqueous NH4Cl, the mixture was partitioned between EtOAc and water. Aqueous layer was extracted with EtOAc (3×). Combined organic phase was washed with brine and dried over anhydrous MgSO4. Concentration was followed by purification by flash chromatography (hexanes:EtOAc=1:1, then 100% EtOAc) to give the title compound as a foamy solid. 1HNMR (500 MHz, CDCl3) δ 1.26 (t, 3H, J=7.4 Hz), 1.49 (s, 9H), 1.75–1.90 (m, 4H), 1.90–2.10 (m, 4H), 2.76 (q, 2H, J=7.6 Hz), 2.89 (t, 2H, J=6.4 Hz), 3.10–3.20 (br, 2H), 3.85–4.05 (br, 2H), 4.09 (t, 2H, J=6.2 Hz). ESI-MS 276 (M-tert-Bu-H2O+H); HPLC A 2.05 min.

Provenance & Evidence