تفاعل #1702108

معادلة التفاعل

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

المردود 90.2%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىthe resulting mixture was degassed with nitrogen for an additional 5 minutes after which the reaction
2. 2
   أخرىwas placed in a 80° C.
3. 3
   درجة الحرارةheated for 3.5 h
4. 4
   درجة الحرارةThe reaction was cooled
5. 5
   أخرىpartitioned between ethyl acetate and sat. NaHCO3
6. 6
   أخرىThe organic layer was separated
7. 7
   غسيلwashed with 5% LiCl, brine
8. 8
   تجفيفdried over Na2SO4
9. 9
   تركيزconcentrated
10. 10
    أخرىto give a dark brown foam
11. 11
    أخرىPurification by flash column chromatography on silica gel using 30% ethyl acetate in hexanes

الإجراء التجريبي

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.

المصدر