Reaktion #1133632

Reaktionsgleichung

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

Ausbeute 90.2%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
2. 2
   Sonstigewas placed in a 80° C.
3. 3
   Temperaturheated for 3.5 h
4. 4
   TemperaturThe reaction was cooled
5. 5
   Sonstigepartitioned between ethyl acetate and sat. NaHCO3
6. 6
   SonstigeThe organic layer was separated
7. 7
   Waschenwashed with 5% LiCl, brine
8. 8
   Trocknendried over Na2SO4
9. 9
   Einengenconcentrated
10. 10
    Sonstigeto give a dark brown foam
11. 11
    SonstigePurification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes

Vorschrift

A solution of the 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.

Quelle