Organic Chemistry of Drug Synthesis. Volume 7

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

1. [O]


2. BH 3 ,Aux.
   CH 3 O

OTHP

OTMBDS

3. TMBDSCl

Co(CO) 8

94

CH 3 O

O OTHP

OTMBDS

95

H 2

CH 3 O

O 96 OTHP

1. NaBH 4
   2H+.

CH 3 O

OH OH

HO

OH OH

97

O

OH OH

HO 2 C

99 98

REFERENCES

1. A. Karjalainen, P. Huhtala, S. Wurster, M. Eloranta, M. Hillila, R. Saxlund,
   V. Cockroft, A. Karjalainen, U.S. Patent 6,313,322 B1 (2001).


2. M. Fuji, T. Suzuki, S. Hayashibe, S. Tsukamoto, S. Yatsugi, T. Yamaguchi,
   U.S. Patent 5,521,180 (1996).


3. Y. Imura, M. Mishima, M. Sugimoto,J. Label. Comp. Radiopharm 27 , 835
   (1989).

REFERENCES 81