反应详情

A stirred suspension of 8.87 g of 2-amino-N-formyl-N-methyl-α-(3-methyl-2-thienyl)benzeneethanamine and 71 ml of 50% (w/v) sulfuric acid was chilled with an ice water bath for 15 minutes. The suspension was treated dropwise over one minute with a solution of sodium nitrite (2.45 g) and water (13 ml). After stirring with chilling for 15 minutes, the mixture was strained through glass wool into a dropping funnel and then added over a few minutes to a refluxing solution of 63.84 g of copper sulfate and 130 ml of water. After a few minutes of vigorous stirring, the reaction mixture was cooled to room temperature with an ice bath, diluted with water and dichloromethane and transferred to a separatory funnel. The phases were separated and the aqueous phase was extracted with dichloromethane (2×200 ml). The combined organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to an oil. The oil was purified by means of preparative HPLC (Water's Associates Prep LC/System 500, silica gel, sample applied in dichloromethane and eluted with ethyl acetate-hexane (1:1)). The appropriate fractions were combined and concentrated to an oil which crystallized on refrigerated storage overnight. Recrystallization from ethyl acetate (20 ml) afforded 1.62 g of N-formyl-2-hydroxy-N-methyl-α-(3-methyl-2-thienyl)benzeneethanamine, mp 142°-144° C.

1. temperaturewas chilled with an ice water bath for 15 minutes
2. temperaturewith chilling for 15 minutes
3. customthe mixture was strained through glass wool into a dropping funnel
4. waitAfter a few minutes of vigorous stirring
5. customtransferred to a separatory funnel
6. customThe phases were separated
7. extractionthe aqueous phase was extracted with dichloromethane (2×200 ml)
8. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated to an oil
11. customThe oil was purified by means of preparative HPLC (Water's Associates Prep LC/System 500, silica gel, sample applied in dichloromethane and eluted with ethyl acetate-hexane (1:1))
12. concentrationconcentrated to an oil which
13. customcrystallized on refrigerated storage overnight
14. customRecrystallization from ethyl acetate (20 ml)