反应详情

As described with reference to Reaction Scheme I, compounds of Formula 2 can be converted to the intermediates of Formula 3 according to the procedure described by Belletire, et al. [Synthetic Commun., 12(10), 763-770 (1982)]. For example, to a 250 ml single neck round bottom reaction flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet, is added 6.0 g (21.79 mmol) of 1-cyano-1-trimethylsiloxy-6-methoxy-1,2,3,4-tetrahydronaphthalene. In one portion, 20.0 g (88.6 mmol) stannous chloride decahydrate followed by 20 ml glacial acetic acid and 20 ml concentrated hydrochloric acid is added. The reaction apparatus is immediately flushed with nitrogen and plunged into a preheated (140° C.) oil bath. With vigorous stirring the reaction mixture is heated at reflux for 65 hours, cooled to room temperature, diluted with 250 ml chloroform, the layers separated, and the aqueous layer again extracted with chloroform. The combined organic layers are extracted three times with 2N aqueous KOH, and the combined basic aqueous layers back-extracted with ether. The basic aqueous layer is acidified with ice-bath cooling, extracted three times with chloroform, the organic layers dried over magnesium sulfate, filtered, and the volatiles removed to give 6-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid, an intermediate of Formula 3, as a crystalline solid.

1. temperaturereflux condenser and nitrogen inlet
2. additionis added
3. customThe reaction apparatus is immediately flushed with nitrogen
4. customplunged into a preheated (140° C.) oil bath
5. temperatureis heated
6. temperatureat reflux for 65 hours
7. additiondiluted with 250 ml chloroform
8. customthe layers separated
9. extractionthe aqueous layer again extracted with chloroform
10. extractionThe combined organic layers are extracted three times with 2N aqueous KOH
11. extractionthe combined basic aqueous layers back-extracted with ether
12. customThe basic aqueous layer is acidified with ice-bath
13. temperaturecooling
14. extractionextracted three times with chloroform
15. dry with materialthe organic layers dried over magnesium sulfate
16. filtrationfiltered
17. customthe volatiles removed