Ethyl diazoacetate → Ethyl 5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazole-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

CuCN (1.74 g, 19.4 mmol) and LiCl (4.95 g, 117.0 mmol) were dried under high vacuum with stirring at 160° C. overnight and then cooled to room temperature. To a solution of 2-(3-butynyloxy)tetrahydro-2H-pyran (3.1 mL, 19.5 mmol) in THF at −78° C. (40.0 mL) was added n-BuLi (12.2 mL, 19.4 mmol, 1.6M solution in hexane). The resulting solution was stirred at −78° C. for 1 h and then transferred to a −78° C. suspension of CuCN.6LiCl (6.70 g, 19.5 mmol, from above) in THF (60.0 mL). The resulting reaction mixture was warmed to −17° C. (dry ice/brine) and stirred for 1.5 h. A solution of ethyl diazoacetate (2.0 mL, 19.4 mmol) in THF (40.0 mL) was then added, and the reaction mixture was stirred at −17° C. for 30 min. The ice bath was removed and stirring was continued at room temperature for 4 h. The reaction mixture was quenched with sat. aq. NH4Cl solution and extracted with Et2O (3×). The combined organic extracts were washed with sat. aq. NaCl solution and then dried over MgSO4, filtered and concentrated in vacuo. The crude oil was purified using flash column chromatography to give the title compound (2.76 g, 53%). 1H NMR (DMSO-d6) δ 6.55 (br s, 1H), 4.64-4.53 (m, 1H), 4.24 (q, J=7.0 Hz, 2H), 3.83 (td, J=9.7, 6.8 Hz, 1H), 3.72-3.53 (m, 2H), 3.47-3.34 (m, 1H), 2.88 (t, J=6.3 Hz, 2H), 1.76-1.52 (m, 2H), 1.51-1.35 (m, 4H), 1.27 (t, J=7.0 Hz, 3H); MS(ESI+) m/z 269.2 (M+H)+.

Provenance & Evidence