Hydrochloric Acid → 2-Fluoro-4-methoxyaniline

HRID 2225376Notes

Reaction equation

HRID 2225376 reaction equation
N([O-])=O.[Na+].[ClH:5].[Sn](Cl)Cl.NN.CCOC(C1C(=O)CCCC1)=O.[F:23][C:24]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:25]=1[N:32]1[C:40](=O)[C:39]2[CH2:38][CH2:37][CH2:36][CH2:35][C:34]=2[NH:33]1>P(Cl)(Cl)(Cl)=O.C(O)(=O)C>[F:23][C:24]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:25]=1[NH2:32].[Cl:5][C:40]1[N:32]([C:25]2[CH:26]=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:24]=2[F:23])[N:33]=[C:34]2[C:39]=1[CH2:38][CH2:37][CH2:36][CH2:35]2

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 9321HydrazineHCID 24479Stannous ChlorideHCID 95543Ethyl 2-oxocyclohexanecarboxylateHCID 189810182-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-oneHCID 23668193Sodium Nitrite

Product 2

HCID 37563832-Fluoro-4-methoxyanilineHCID 189810153-Chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 24813Phosphorus oxychlorideSolvent

Procedure

The diazonium salt of 2-fluoro-4-methoxyaniline was prepared using sodium nitrite and hydrochloric acid and was then reduced in situ with tin(II) chloride to prepare the correspondingly substituted phenylhydrazine (XIX). Reaction of this hydrazine with ethyl 2-cyclohexanonecarboxylate and subsequent heating of the product in the presence of acetic acid produced a mixture of 2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-one (XX) and the 2-fluoro-4-methoxyphenylhydrazone of 2-cyclohexanonecarboxylic acid. This mixture was heated in phosphorus oxychloride, yielding 3-chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole (XXI), which was then cleaved with boron tribromide to the desired 3-chloro-2-(2-fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydroindazole (XXII). ##STR14##

Workup

  1. customproduced

Sources & evidence

ORD record
ord-d85f43902bbb422eb817c12891d5afb9
Source dataset
uspto-grants-1994_09
Patent number
US05344812

Reaction notes

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