反応 #1702108

反応方程式

3,3-dimethyl-pent-4-yn-1-ol

3-[[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester

triethylamine

→

3-[[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-(5-hydroxy-3,3-dimethyl-pent-1-ynyl)-thiophene-2-carboxylic acid methyl ester

収率 90.2%

溶媒

DMF

反応条件

後処理

1. 1
   その他the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
2. 2
   その他was placed in a 80° C.
3. 3
   温度heated for 3.5 h
4. 4
   温度The reaction was cooled
5. 5
   その他partitioned between ethyl acetate and sat. NaHCO3
6. 6
   その他The organic layer was separated
7. 7
   洗浄washed with 5% LiCl, brine
8. 8
   乾燥dried over Na2SO4
9. 9
   濃縮concentrated
10. 10
    その他to give a dark brown foam
11. 11
    その他Purification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes

実験手順

A solution of 3,3-dimethyl-pent-4-yn-1-ol (600 mg, 5.36 mmol), 3-[[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester (2767 mg, 4.46 mmol) and triethylamine (10.8 mL, 77.48 mmol) in DMF (25 mL) was degassed for 10 minutes with nitrogen. PdCl2(PPh3)2 (314 mg, 0.45 mmol) and CuI (170 mg, 0.90 mmol) was added and the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction was placed in a 80° C. oil bath and heated for 3.5 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 brown foam. Purification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes then 5% methanol in ethyl acetate provided 3-[[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-(4-methyl-cyclohexanecarbonyl)-amino]-5-(5-hydroxy-3,3-dimethyl-pent-1-ynyl)-thiophene-2-carboxylic acid methyl ester (2.43 g, 90%) as a pale yellow foam.

出典