the phenol ( 98 ) is obtained by treatment of 97 with butyllithium and diph-
enylphosphine. The product ( 98 ) is then alkylated with 2-chloroacetonitrile.
Hydrolysis of the cyano group to an acid finally affords the vasodilator
treprostinil( 99 ).14–16
O
CO 2 H
HO OH
100
OH
CH 3 O
88
OTMBDS
CH 3 O
89
TMBDS = tBuMe 2 Si-
Br
BuLi
OH
CH 3 O
90
[O] CH=O
CH 3 O
91
OTHP 92
CH 3 O
OTHP
OH
93 , THP = tetrahydropyranyl
- [O]
- BH 3 ,Aux.
CH 3 O
OTHP
OTMBDS
- TMBDSCl
Co(CO) 8
94
CH 3 O
O OTHP
OTMBDS
95
H 2
CH 3 O
O 96 OTHP
- NaBH 4
2H+.
CH 3 O
OH OH
HO
OH OH
97
O
OH OH
HO 2 C
99 98
REFERENCES
- A. Karjalainen, P. Huhtala, S. Wurster, M. Eloranta, M. Hillila, R. Saxlund,
V. Cockroft, A. Karjalainen, U.S. Patent 6,313,322 B1 (2001). - M. Fuji, T. Suzuki, S. Hayashibe, S. Tsukamoto, S. Yatsugi, T. Yamaguchi,
U.S. Patent 5,521,180 (1996). - Y. Imura, M. Mishima, M. Sugimoto,J. Label. Comp. Radiopharm 27 , 835
(1989).
REFERENCES 81