Hydrazine hydrate (1:1) → 6-butyl-5-(4-cyclohexyloxy-phenyl)-4-trifluoromethyl-2H-pyridazin-3-one

HRID 401972Notes

Reaction equation

C[O:2][C:3](=O)[C:4]([C:25]([F:28])([F:27])[F:26])=[C:5]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:14][CH:13]=1)[C:6](=O)[CH2:7][CH2:8][CH2:9][CH3:10].O.[NH2:31][NH2:32]>C(O)(=O)C>[CH2:7]([C:6]1[C:5]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:14][CH:13]=2)=[C:4]([C:25]([F:28])([F:27])[F:26])[C:3](=[O:2])[NH:31][N:32]=1)[CH2:8][CH2:9][CH3:10]

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred solution of 3-(4-cyclohexyloxy-phenyl)-4-oxo-2-trifluoromethyl-oct-2-enoic acid methyl ester (3.40 mmol, 1.4 g) in glacial acetic acid (3 mL) was added hydrazine hydrate (61.7 mmol, 3 mL) and the reaction was heated at 100° C. for 12 h. After cooling, the volatiles were under reduced pressure to give 1.6 g of crude 6-butyl-5-(4-cyclohexyloxy-phenyl)-4-trifluoromethyl-2H-pyridazin-3-one. The ketone was treated with phosphorous oxychloride (21.8 mmol, 2.0 mL) and heated at 90° C. for 1 hour with stirring. The reaction mixture was cooled to room temperature and the volatiles were removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and shaken with water (30 mL). The layers were separated and the organic layer was washed with saturated NaHCO3 (2×30 mL), brine (30 mL), dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was purified on a 40 g SiO2 cartridge eluting with ethyl acetate/hexanes gradient to afford 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-5-trifluoromethyl-pyridazine (0.65 g).

Workup

temperatureAfter cooling

Sources & evidence

ORD record: ord-679a7b3526c547e389d6378122e3fd51
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08741900B2

Reaction notes

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