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8715279 
Journal Article 
Rhodium catalyzed hydroformylation of 1,1-bis(p-fluorophenyl)allyl or propargyl alcohol: A key step in the synthesis of Fluspirilen and Penfluridol 
Botteghi, C; Marchetti, M; Paganelli, S; Persi-Paoli, F 
2001 
1 
Tetrahedron
ISSN: 0040-4020 
57 
8 
1631-1637 
English 
Fluspirilen (1) and Penfluridol (2), two neuroleptic agents, belong to a wide class of pharmaceuticals that contain in their molecules a 4,4-bis(p-fluorophenyl)butyl group bound to a nitrogen atom of a pyrrolidine, piperidine or piperazine moiety. A key intermediate for the synthesis of compounds 1 and 2,4,4-bis(p-fluorophenyl)butylbromide (15), has been prepared starting from commercially available 4,4′-difluorobenzophenone (7) following a preparative route involving the rhodium catalyzed hydroformylation in toluene or in the biphasic system toluene/water or cyclohexane/water of 1,1-bis(p-fluorophenyl)-2-propenol (8) and/or 1,1-bis(p-fluorophenyl)-2-propynol (12). Fluspirilen and Penfluridol were obtained in 70-80% yield by reaction of bromide 15 with 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one (16) and 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol (17), respectively. The overall yields of the two pharmaceuticals 1 and 2, based on starting ketone 7, were about 35-40%. 2001 Published by Elsevier Science Ltd. 
Fluspirilen; Hydroformylation; Penfluridol