反应详情

温度

40 °C

To a 25 mL RBF under nitrogen, 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (1 eq.), copper iodide (0.025 eq.) and tris(dibenzylideneacetone)dipalladium (0) (0.01 eq.) are taken. DMF, triethylamine (2.5 eq.) and 3,3-dimethyl-but-1-yne (2 eq.) are added and the reaction mixture is stirred at 40° C. for 2 h under a N2 atmosphere. The reaction mixture is filtered on celite and washed with ethyl acetate. The solution is diluted with water and extracted 2 times with ethyl acetate. The organic phases are combined and washed 3 times with water. The organic layer is separated, dried (Na2SO4), evaporated to about 2 mL and then 8 mL of heptane is added. It is evaporated to 2-4 mL and cooled in an ice bath. The formed white solid is filtered, washed with heptane and dried in oven to obtain 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester.

1. filtrationThe reaction mixture is filtered on celite
2. washwashed with ethyl acetate
3. additionThe solution is diluted with water
4. extractionextracted 2 times with ethyl acetate
5. washwashed 3 times with water
6. customThe organic layer is separated
7. dry with materialdried (Na2SO4)
8. customevaporated to about 2 mL
9. addition8 mL of heptane is added
10. customIt is evaporated to 2-4 mL
11. temperaturecooled in an ice bath
12. filtrationThe formed white solid is filtered
13. washwashed with heptane
14. customdried in oven