反应详情

温度

80 °C

A 3-neck round-bottom flask fitted with a reflux condenser was charged with dioxane (8.5 mL) and aqueous CsF (7.65 mL, 1M solution, 7.65 mmol). This was heated to 80° C. for 0.5 h under nitrogen atmosphere. After 30 min, Preparation 24, tert-butyl (3R)-3-{(3-methylpyridin-2-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]amino}piperidine-1-carboxylate (1.66 g, 3.19 mmol) was added followed by Preparation 23a, (S)-ethyl 1-[5-(4-iodo-1-methyl-1H-pyrazol-5-yl)-2H-tetrazol-2-yl]ethyl carbonate (1.00 g, 2.55 mmol), and Pd(amphos)Cl2 catalyst (90.6 mg, 0.128 mmol). The reaction was stirred at 80° C. for 5.5 h. Aqueous ammonium chloride solution (10 mL) was added followed by EtOAc (10 mL). The layers were separated, and the aqueous phase was further extracted with EtOAc (3×15 mL), dried with MgSO4, passed through a plug of silica, and concentrated. The crude material was purified via MPLC using a gradient of 20-70% EtOAc/heptane to afford tert-butyl (3R)-3-[{4-[5-(2-{(1S)-1-[(ethoxycarbonyl)oxy]ethyl}-2H-tetrazol-5-yl)-1-methyl-1H-pyrazol-4-yl]benzoyl}(3-methylpyridin-2-yl)amino]piperidine-1-carboxylate as a colorless solid (1.05 g, 77%). 1H NMR (CDCl3) δ: 8.41 (d, 1H), 7.61 (s, 1H), 7.36-7.32 (m, 1H), 7.24-7.10 (m, 6H), 4.76-4.46 (m, 2H), 4.32 (q, 2H), 4.07 (s, 3H), 3.47-3.36 (m, 1H), 2.67-2.14 (m, 3H), 2.06-1.99 (m, 6H), 1.81-1.59 (m, 3H), 1.47 (s, 9H), 1.36 (t, 3H).

1. customA 3-neck round-bottom flask fitted with a reflux condenser
2. additionwas added
3. customThe layers were separated
4. extractionthe aqueous phase was further extracted with EtOAc (3×15 mL)
5. dry with materialdried with MgSO4
6. concentrationconcentrated
7. customThe crude material was purified via MPLC