Tetrahydrofuran → methyl 3-[(4-bromo-1H-pyrazol-1-yl)methyl]benzoate

To a solution of 4-bromo-1H-pyrazole (1.00 g, 6.80 mmol) in DMF (11.7 mL) at 0° C. was added 1 M solution of NaHMDS in THF (7.48 mL, 7.48 mmol) slowly over 2 min. The reaction mixture was stirred for 10 min and then the cooling bath was removed. After 30 min a solution of methyl 3-(bromomethyl)benzoate (1.71 g, 7.48 mmol) in DMF (1.9 mL) was added slowly, and the resulting mixture was stirred at room temperature overnight. At the conclusion of this period, the reaction mixture was quenched with saturated aq ammonium chloride (˜1 mL), and partitioned between diethyl ether and water. The resulting mixture was stirred vigorously for 15 min. After this time, the organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by flash chromatography (0-60% ethyl acetate:hexanes) to afford the title compound (1.59 g, 79%). LCMS, [M+H]+=295.0. 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J=7.1 Hz, 1H), 7.94 (s, 1H), 7.50 (s, 1H), 7.47-7.36 (m, 3H), 5.31 (s, 2H), 3.92 (s, 3H).

1. customthe cooling bath was removed
2. stirringthe resulting mixture was stirred at room temperature overnight
3. customAt the conclusion of this period, the reaction mixture was quenched with saturated aq ammonium chloride (˜1 mL)
4. custompartitioned between diethyl ether and water
5. stirringThe resulting mixture was stirred vigorously for 15 min
6. customAfter this time, the organic layer was separated
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe resulting residue was purified by flash chromatography (0-60% ethyl acetate:hexanes)

ORD record

ord-6a66aa28cd1c467586e63c3ba20024ab

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062028B2