Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 30

Cardiovascular Medicines/Antihypertensive Medicines

An aromatic ketone is often formed by Friedel–Crafts Acylation.

Discussion. The ether is formed in the final step by displacement of the chloride of 2‐chloro‐N,N‐diethylethanamine by the phenol (Williamson Ether Synthesis).

The phenol is iodinated in both ortho positions. The phenol is formed by demethylation of the ether. The ketone is formed by acylation of 2‐butyl‐2,3‐benzofuran with 4‐methoxybenzoyl chloride (Friedel–Crafts Acylation). 4‐Methoxybenzoyl chloride is formed from para‐anisic acid.

2‐Butylbenzofuran is formed by rearrangement of the chlorohydrin. The tertiary alcohol of the chlorohydrin is formed by addition of butylmagnesium chloride to the ketone (Grignard Reaction). Butylmagnesium chloride is formed from 1‐chlorobutane. 2‐Chloro‐2′‐hydroxyacetophenone is formed from phenol and chloroacetonitrile (Sugasawa Reaction).