1. Studies on Uricosuric Diuretics. V. Convenient and Efficient Synthesis of 2,3-Dihydrobenzofuran Derivatives
- Author
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Bunya Aoki, Hiroshi Koga, Haruhiko Sato, Kiyonori Kuromaru, and Takenori Ishizawa
- Subjects
Potassium hydroxide ,Uricosuric ,Chemistry ,Sulfonium ,Benzisoxazole ,General Chemistry ,General Medicine ,Mannich base ,Medicinal chemistry ,chemistry.chemical_compound ,Sodium hydroxide ,Uricosuric Agent ,Drug Discovery ,Organic chemistry ,Dimethylamine - Abstract
A practical procedure for synthesis of a new uricosuric agent, 5-chloro-7, 8-dihydro-3-phenylfuro[2, 3-g]-1, 2-benzisoxazole-7-carboxylic acid (1, AA-193) is described, which starts from 2, 5-dichlorophenol (3b) and involves 5-chloro-6-hydroxy-3-phenyl-1, 2-benzisoxazole (2) as the key intermediate. Successive treatment of 3b with benzoyl chloride-aluminum chloride (AlCl3) and hot ethanolic sodium hydroxide gives 4-benzoyl-2, 5-dichlorophenol (8, 61%), which is oximated with hydroxylamine hydrochloride and then transformed into the benzisoxazole 2 (88%) with potassium hydroxide in N, N-dimethylformamide (DMF) (method C). The reaction of 2 with aqueous formaldehyde and dimethylamine affords the Mannich base 11a (97%), which is treated with a sulfonium ylide 12, 14 or 15 followed by heating with sodium hydroxide (NaOH) in ethanol (EtOH) to give 1 in high yield (method E).
- Published
- 1992
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