Reacción #1702108

Ecuación de reacción

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

Rendimiento 90.2%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
2. 2
   Otrowas placed in a 80° C.
3. 3
   Temperaturaheated for 3.5 h
4. 4
   TemperaturaThe reaction was cooled
5. 5
   Otropartitioned between ethyl acetate and sat. NaHCO3
6. 6
   OtroThe organic layer was separated
7. 7
   Lavadowashed with 5% LiCl, brine
8. 8
   Secadodried over Na2SO4
9. 9
   Concentraciónconcentrated
10. 10
    Otroto give a dark brown foam
11. 11
    OtroPurification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes

Procedimiento

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.

Fuente