Bromomethylcyclopropane → 1-(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

To a stirred solution of pyrazole-4-boronic acid pinacol ester (0.25 g, 1.29 mmol) in THF (5 mL) was added a solution of sodium bis(trimethylsilyl)amide (0.71 mL, 2M in THF, 1.42 mmol), followed by (bromomethyl)cyclopropane (0.19 mL, 1.93 mmol). The reaction mixture was stirred at r.t. in a sealed tube for 16 h, then at 80° C. for 4 h. Additional (bromomethyl)cyclopropane (0.06 mL, 0.65 mmol) was added. The reaction mixture was stirred at 80° C. for 16 h, then concentrated in vacuo. EtOAc (30 mL) and aqueous sat. NH4Cl (15 mL) were added. The organic fraction was separated, washed with H2O (15 mL), then brine (15 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (0.27 g, 84%) as a clear yellow oil that was used without further purification. δH (CDCl3) 7.82 (1H, s), 7.80 (1H, s), 3.99 (2H, d, J 7.2 Hz), 1.32 (12H, s), 1.32-1.19 (1H, m), 0.70-0.59 (2H, m), 0.42-0.33 (2H, m). LCMS (ES+) 249.0 (M+H)+, RT 3.42 minutes (Method 1).

1. waitat 80° C. for 4 h
2. stirringThe reaction mixture was stirred at 80° C. for 16 h
3. concentrationconcentrated in vacuo
4. additionEtOAc (30 mL) and aqueous sat. NH4Cl (15 mL) were added
5. customThe organic fraction was separated
6. washwashed with H2O (15 mL)
7. dry with materialbrine (15 mL), dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD-Eintrag

ord-cd1dcba22a4a41ff836b1caab36d6406

Quelldatensatz

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08242116B2