Phosphorus oxychloride → 3-Chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[C:18](=O)[C:17]2[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=2[NH:11]1.P(Cl)(Cl)([Cl:22])=O>>[Cl:22][C:18]1[N:10]([C:3]2[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=2[F:1])[N:11]=[C:12]2[C:17]=1[CH2:16][CH2:15][CH2:14][CH2:13]2Participants
3
Procedure
The 4.32 g residue from Step B was mixed at ambient temperature with 5.37 g (0.035 mole) of phosphorus oxychloride until complete dissolution occurred. At this point the reaction mixture was heated at reflux under nitrogen for one hour. The phosphorus oxychloride was evaporated from the reaction mixture under reduced pressure, leaving a residue weighing 1.50 g. This residue, together with a similar residue weighing 0.30 g from an earlier experiment, was then was placed on a silica gel column and eluted with hexane/ethyl acetate (4:1). After the product-containing fractions were combined and the solvents evaporated under reduced pressure, 0.50 g of 3-chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole was isolated. The NMR was consistent with the proposed structure.