USE OF A TITANIUM THIENYL ANION AND A SIMPLE PROCEDURE FOR INTRODUCING A THIOL-GROUP INTO THIOPHENE IN THE DEVELOPMENT OF A MANUFACTURING ROUTE TO THE 5-LIPOXYGENASE INHIBITOR ZD4407
J. Hutton et al., USE OF A TITANIUM THIENYL ANION AND A SIMPLE PROCEDURE FOR INTRODUCING A THIOL-GROUP INTO THIOPHENE IN THE DEVELOPMENT OF A MANUFACTURING ROUTE TO THE 5-LIPOXYGENASE INHIBITOR ZD4407, Organic process research & development, 1(1), 1997, pp. 61-67
Process development has been conducted to identify a synthetic route t
o the 5-lipoxygenase inhibitor ZD4407 that could be used for pilot pla
nt manufacture. Efficient and environmentally acceptable carbon-functi
onalisation of the 3-position of thiophene using readily available 3-b
romothiophene has been achieved using a titanium carbanionic intermedi
ate, An efficient functionalisation of the 5-position with a thiol gro
up has also been realised using dimethyl disulphide, where the side pr
oduct of the functionalisation reaction is used in situ as the reagent
for the subsequent deprotections, thereby considerably reducing the i
mpact on the environment.