3-Bromopyridine → 4-Hydroxy-4-(3-pyridyl)cyclohexanone ethylene acetal

Participants

Reaction Conditions

Reaction Steps

To a solution of n-BuLi (2.5 M in hexanes, 88.4 mL, 221.0 mmol) in Et2O (250 mL) at −78° C. was added a chilled solution (−78° C.) of 3-bromopyridine (35 g, 221.0 mmol) in Et2O (125 mL) via cannula. After being stirred for 10 min, a solution of 1,4-cyclohexanedione monoethylene ketal (34.5 g, 221.0 mmol) in THF (125 mL) was added via cannula The reaction mixture was stirred for 1 h at −78° C., then slowly warmed to −20° C. over 1 h. The reaction was quenched by pouring into saturated aqueous NH4Cl, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (100 mL×3) and the combined organic layers were washed with brine (200 mL), dried with MgSO4 and concentrated in vacuo. The crude product was triturated with Et2O to afford 4-hydroxy-4-(3-pyridyl)cyclohexanone ethylene ketal as a white solid.

Provenance & Evidence