35277-02-2, A common heterocyclic compound, 35277-02-2, name is 4-Fluoro-1H-pyrazole, molecular formula is C3H3FN2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a dry, nitrogen-purged 100 mL round-bottom flask equipped with a dropping funnel under argon atmosphere, NaH of 60% dispersion in mineral oil (674 mg, 16.9 mmol) was added in 60 mL of anhydrous THF solvent in the flask at ice-water bath, and 4-fluoro-1H-pyrazole (691 mg, 8.03 mmol) was stirred in over 30 min at the ice-water bath. Into the flask, the solution of (R)-3-bromo-2- hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (2.98 g, 8.03 mmol) in 10 mL of anhydrous THF was added through dropping funnel under argon atmosphere at the ice-water bath and stirred overnight at room temperature. After adding 1 mL of H2O, the reaction mixture was condensed under reduced pressure, and then dispersed into 50 mL of EtOAc, washed with 50 mL (x 2) water, evaporated, dried over anhydrous MgSO4, and evaporated to dryness. The mixture was purified with flash column chromatography as an eluent EtOAc/hexane = 1/2 to produce designed compound (2.01 g, 67%) as yellowish solid.MS (ESI) m/z 375.08 [M- H]-; 377.22 [M + H] +; 399.04 [M + Na]+;19F NMR (CDCl3, decoupled) d -60.13, -176.47; assigned by NOE and COSY; 1H NMR (400 MHz, CDCl3) d 9.14 (bs, 1H, NH), 8.01 (s, 1H), 7.97-7.91 (m, 2H), 7.38 (d, J = 3.6 Hz, 1H), 7.35 (d, J = 4.4 Hz, 1H), 5.95 (s, 1H, OH), 4.56 (d, J = 14.0 Hz, 1H), 4.17 (d, J = 14.0 Hz, 1H), 1.48 (s, 3H).
The synthetic route of 4-Fluoro-1H-pyrazole has been constantly updated, and we look forward to future research findings.