4-Piperidone → 5-Chloro-1-(4-fluorophenyl)-3-(piperidin-4-yl)-1H-indole

HRID 1250028Notes

Reaction equation

HRID 1250028 reaction equation
[CH:1]1[C:6]([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([Cl:16])=[CH:15][C:10]=3[C:9]([CH:17]3[CH2:22][CH2:21][N:20](CCN4C(=O)NCC4)[CH2:19][CH2:18]3)=[CH:8]2)=[CH:5][CH:4]=[C:3]([F:31])[CH:2]=1.ClC1C=C2C(=CC=1)N(C1C=CC(F)=CC=1)C=C2.N1CCC(=O)CC1.ClC1C=C2C(=CC=1)N(C1C=CC(F)=CC=1)C=C2C1CCNCC=1>FC(F)(F)C(O)=O.C(O)(=O)C>[Cl:16][C:14]1[CH:15]=[C:10]2[C:11](=[CH:12][CH:13]=1)[N:7]([C:6]1[CH:5]=[CH:4][C:3]([F:31])=[CH:2][CH:1]=1)[CH:8]=[C:9]2[CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 337214-PiperidoneHCID 60149SertindoleHCID 98838385-Chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 102361885-Chloro-1-(4-fluorophenyl)-1H-indole

Product 1

HCID 98622725-Chloro-1-(4-fluorophenyl)-3-(piperidin-4-yl)-1H-indole

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Perregaard et al., J Med. Chem, 1992, 35, 1092-1101, disclosed a new method of preparing sertindole. This method comprises reaction of the intermediate 5-chloro-1-(4-fluorophenyl)indole with 4-piperidone in a mixture of trifluoroacetic acid and acetic acid, reduction of the resulting 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole in order to obtain 5-chloro-1-(4-fluorophenyl)-3-(piperidin-4-yl)indole which in turn is reacted with 1-(2-chloroethyl)-2-imidazolidinon in the presence of K2CO3 and KI in methyl isobutyl ketone (MIBK). The 5-chloro-1-(4-fluorophenyl)indole was obtained from the corresponding 3-acetoxy-indole by NaBH4 reduction in methanol and subsequent elimination of H2O under acidic conditions. The 3-acetoxy-indole was prepared from the N-(4fluorophenyl)-N-(2-carboxy-4-chlorophenyl)glycine following literature procedures.

Sources & evidence

ORD record
ord-6ccee11dc8b64e969155ec1beffe58b6
Source dataset
uspto-grants-2002_01
Patent number
US06335463B1

Reaction notes

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