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Anal. Calc. for C9H10N2O2Cl2 -0.1 C6H12:C, 44.78; H, 4.38; N, 10.89 Found: C, 44.63; H, 4.22; N, 10.94 B. 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 hexanes/ethyl 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° C.-120° C. Anal. Calc. for C10H13N2O3Cl: C,49.09; H,5.36; N,11.45 Found: C,49.04; H, 5.38; N, 11.43 C. 4-Chloro-5-methoxy-2-(tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone (2486 g, 10.16 moles), ethanol (8L), triethylamine (2L, 14.23 moles) and 5% Pd-C (100 g of 50% water-wet Pd-C) were added to a 0.019 stere autoclave. The mixture was hydrogenated at 345-414 kilo Pascals of H2 and heated to a maximum temperature of 43° C. After 24 h, the reaction was complete. The reaction mixture was diluted with a small amount of water and vacuum filtered through celite. The aqueous phase was extracted with ethyl acetate (2×2 L). The combined organics were washed with 5 L brine, dried (MgSO4), and vacuum filtered. The solution was concentrated in-vacuo to give 2133 g (100% yield) of 5-methoxy-2- (tetrahydro-2H-pyran-2-yl)-3(2H)-pyridazinone as a dark oil which later crystallized to give a tan product suitable for further transformations. The product was purified by recrystallization from ethyl acetate/cyclohexane to give a white solid, mp=76° C.-78° C.

1. customexothermed to 40° C
2. additionthe addition the mixture
3. customThe reaction mixture was partitioned with 12 L of ethyl acetate and 12 L of H2O
4. extractionThe aqueous layer was extracted with ethyl acetate (2×4 L)
5. washThe combined organic layers were washed with brine (2×10 L)
6. dry with materialdried (MgSO4)
7. filtrationThe organic solution was clarified by filtration
8. concentrationconcentrated
9. customto give a dark semi-solid
10. filtrationfiltered on a Buchner funnel and air
11. customdried overnight