Methanol → 4-Chloro-5-methoxy-2-(2-tetrahydropyranyl)pyridazin-3(2H)-one

Participants

Reaction Conditions

Reaction Steps

4,5-Dichloro-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone from the previous step and 17 L of methanol were added to a 50 L round bottomed flask equipped with a glycol cooling jacket and a mechanical stirrer. The resulting solution was cooled to 0° C. and 87% KOH (1172 g 18.17 moles) was added in portions over approximately 1 h. The mixture exothermed to 40° C. Following the addition the mixture was allowed to stir an additional 3 h at ambient temperature. The reaction mixture was partitioned with 12 L of ethyl acetate and 12 L of H2O. The aqueous layer was extracted with ethyl acetate (2×4 L). The combined organic layers were washed with brine (2×10 L) and dried (MgSO4). The organic solution was clarified by filtration and concentrated to give a dark semi-solid. The crude material was equally divided and added to two 22 L flasks. The material was suspended in 12 L hexane/diethyl ether (2:1 ratio). The washed material was vacuum filtered on a Buchner funnel and air dried overnight to give 3,406 g (77% over 2 steps) of 4-chloro-5-methoxy-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone as a dark tan solid suitable for further transformations. The product was purified by recrystallization from ethyl acetate/cyclohexane to give a white solid, mp=118°-120° C.

Provenance & Evidence