Phosphorus oxychloride → 3-Chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole

HRID 257373Notes

Reaction equation

HRID 257373 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]2

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 189810182-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-one

Product 1

HCID 189810153-Chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazoleYield 10.8%

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.

Workup

  1. temperatureAt this point the reaction mixture was heated
  2. temperatureat reflux under nitrogen for one hour
  3. customThe phosphorus oxychloride was evaporated from the reaction mixture under reduced pressure
  4. customleaving a residue
  5. washeluted with hexane/ethyl acetate (4:1)
  6. customthe solvents evaporated under reduced pressure

Sources & evidence

ORD record
ord-a25573057d1a41158da0b3251348b73e
Source dataset
uspto-grants-1993_11
Patent number
US05262390

Reaction notes

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