反应详情

To a solution of 1-[2,2-dimethyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl]-4-iodo-1H-pyrazole (Compound 47D, 539 mg, 1.48 mmol) in THF (20 mL) was added 1.3 M of i-PrMgCl.LiCl in THF (2.28 mL, 2.96 mmol) at 0° C. The reaction was allowed to warm gradually to rt over 20 min. 2-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.73 mL, 4.44 mmol) was added and the mixture was stirred at rt for 16 hrs. The reaction mixture was quenched with water and then extracted with EtOAc. The organic layer was washed with water, brine (2×), dried over sodium sulfate, filtered, concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0-40% Acetone/Heptanes] to afford 500 mg the desired product (100%). 1H NMR (400 MHz, CD3OD) δ 7.81 (s, 1H), 7.65 (s, 1H), 4.58 (d, J=2.8 Hz, 1H), 4.14 (s, 2H), 3.80-3.91 (m, 1H), 3.46-3.54 (m, 1H), 3.44 (d, J=9.6 Hz, 1H), 3.02 (d, J=9.3 Hz, 1H), 1.80-1.97 (m, 1H), 1.68-1.79 (m, 1H), 1.49-1.67 (m, 5H), 1.31 (s, 10H), 0.87-0.98 (m, 6H), 0.84-1.01 (m, 1H). MS (ESI): m/z=365.51 [M+H]+. UPLC: tR=1.54 min (UPLC-TOF: polar—2 min).

1. customat 0° C
2. customThe reaction mixture was quenched with water
3. extractionextracted with EtOAc
4. washThe organic layer was washed with water, brine (2×)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. custompurified