Dimethylformamide dimethyl acetal → Methyl 1-[4-(benzyloxy)-2-fluorophenyl]-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylate
Reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][N:16]=[C:17]([C:22](=[O:26])[CH2:23][O:24][CH3:25])[C:18]([O:20][CH3:21])=[O:19])=[C:11]([F:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28]OC(OC)N(C)C>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH:28]=[C:23]([O:24][CH3:25])[C:22](=[O:26])[C:17]([C:18]([O:20][CH3:21])=[O:19])=[N:16]2)=[C:11]([F:27])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Procedure
A solution of methyl 2-{[4-(benzyloxy)-2-fluorophenyl]hydrazono}-4-methoxy-3-oxobutanoate (8.46 g, 22.6 mmol) in N,N-dimethylformamide dimethyl acetal (80 mL) was refluxed for 3 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was diluted with AcOEt, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with THF and recrystallized from hexane/THF to give the title compound (8.12 g, 93% yield) as a white solid: mp 143-144° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.89 (3H, s), 3.96 (3H, s), 5.12 (2H, s), 6.83-6.91 (2H, m), 7.33-7.44 (5H, m), 7.48-7.54 (1H, m), 7.69 (1H, d, J=2.3 Hz). Anal. Calcd for C20H17FN2O5: C, 62.50; H, 4.46; N, 7.29. Found: C, 62.40; H, 4.59; N, 7.26.
Workup
- concentrationthe reaction mixture was concentrated under reduced pressure
- additionThe residue was diluted with AcOEt
- washwashed with water and brine
- dry with materialdried over MgSO4
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel column chromatography
- washeluting with THF
- customrecrystallized from hexane/THF
Sources & evidence
- ORD record
- ord-d785f85c2f3f42ce9c88380ad2f3fc2c
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354411B2
Reaction notes
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