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

HRID 2168700Notes

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-9a242ef486f74903b8846e917212d1cd
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045461B2

Reaction notes

Loading…