反应详情

A solution of 2-(2,2-dimethyl-but-3-ynyloxy)-tetrahydro-pyran (147 mg, 0.806 mmol), 3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (326 mg, 0.645 mmol) and triethylamine (1.0 mL, 7.17 mmol) in DMF (1.0 mL) was degassed for 10 minutes with nitrogen. PdCl2(PPh3)2 (20 mg, 0.028 mmol) and CuI (5.0 mg, 0.026 mmol) was added and the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction was in a 60° C. oil bath and heated for 4 h. The reaction was cooled and partitioned between ethyl acetate and sat. NaHCO3. The organic layer was separated, washed with 5% LiCl, brine, dried over Na2SO4 and concentrated to give a dark orange-brown foam. Purification by flash column chromatography on silica gel using 20% hexanes in ethyl acetate provided the desired product (251 mg, 69%) as a pale yellow foam.

1. customthe resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
2. customwas in a 60° C.
3. temperatureheated for 4 h
4. temperatureThe reaction was cooled
5. custompartitioned between ethyl acetate and sat. NaHCO3
6. customThe organic layer was separated
7. washwashed with 5% LiCl, brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customto give a dark orange-brown foam
11. customPurification by flash column chromatography on silica gel using 20% hexanes in ethyl acetate