반응 #1702108

반응 방정식

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

수율 90.2%

용매

DMF

반응 조건

후처리

1. 1
   기타the resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
2. 2
   기타was placed in a 80° C.
3. 3
   온도heated for 3.5 h
4. 4
   온도The reaction was cooled
5. 5
   기타partitioned between ethyl acetate and sat. NaHCO3
6. 6
   기타The organic layer was separated
7. 7
   세척washed with 5% LiCl, brine
8. 8
   건조dried over Na2SO4
9. 9
   농축concentrated
10. 10
    기타to give a dark brown foam
11. 11
    기타Purification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes

실험 절차

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.

출처