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

HRID 1734995Notes

Reaction equation

HRID 1734995 reaction equation
[Cl:1][C:2]1[C:3](=[O:15])[N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:5]=[CH:6][C:7]=1Cl.[CH3:16][OH:17].[OH-].[K+]>CCCCCC.C(OCC)C>[Cl:1][C:2]1[C:3](=[O:15])[N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:5]=[CH:6][C:7]=1[O:17][CH3:16]

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

Product 1

HCID 106103354-Chloro-5-methoxy-2-(2-tetrahydropyranyl)pyridazin-3(2H)-oneYield 77%

Reagents, catalysts & solvents 1

HCID 21584099Diethylether hexaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-2361e914713046d8b942a9ae452fdc3b
Source dataset
uspto-grants-1996_07
Patent number
US05536701

Reaction notes

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