Labelling of neuroleptic butyrophenones. 1. syntheses of haloperidol-14C and trifluperidol-14C

✍ Scribed by Iwao Nakatsuka; Kazuo Kawahara; Takeshi Kamada; Akira Yoshitake

• Publisher: John Wiley and Sons
• Year: 1978
• Tongue: French
• Weight: 316 KB
• Volume: 14
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580140117

✦ Synopsis

4-[4-(4-Chlorophen y l ) -4-hydroxypiperidinol -4 ' -f l u o r o b u t y r op h e n o n e ( h a l o p e r i d o l ) ( I ) and 4'-fluoro-4-[4-hydroxy-4-(3-trif 1 u o r o m e t h y l p h e n y l ) p i p e r i d i n o l b u t y r o p h e n o n e ( t r i f 1 u p e r i d o f ) (11) , n e u r o l e p t i c d r u g s , were l a b e l l e d a t the c a r b o n y l p o s i t i o n w i t h carbon-14 f o r the u s e of m e t a b o l i c s t u d i e s . T h e s y n t h e s e s w e r e a c h i e v e d a c c o r d i n g t o the r e a c t i o n scheme shown i n F i g . 1 . C y ~l o p r o p i o n i c -l -~~C a c i d ( I V ) was p r e p a r e d f r o m c y c l o p r o p y l b r o m i d e ( I I I ) b y G r i g n a r d r e a c t i o n w i t h carbon-14C d i o x i d e . C o n d e n s a t i o n of I V w i t h f l u o r o b e n z e n e , f o l l o w e d b y r i n g -o p e n i n g w i t h h y d r o g e n c h l o r i d e , g a v e 4-chloro-l'-fluorobutyrophenone-l-1 4 C ( V I )

.

d e n s e d w i t h c o r r e s p o n d i n g p i p e r i d i n e d e r i v a t i v e s ( V I I I a and V I I I b ) a n d s u b s e q u e n t l y h y d r o l i z e d w i t h h y d r o c h l o r i c a c i d t o g i v

e h a l o p e r i d o l -1 -C ( I ) a n d t r i f l u p e r i d o l -1 -C ( I I ) , r e s p e c t i v e l y . The o v e r a l l r a d i o c h e m i c a l y i e l d s o f I and 11 f r o m b a r i u m c a r b on a t e -1 4 C w e r e 31 and 2 7 9 , r e s p e c t i v e l y .

A f t e r k e t a l i z a t i o n o f V I , the k e t a l ( V I I ) was con-1 4 14