反应详情

Cyclohexylmethanol (0.50 mL, 4.06 mmol) was added to a suspension of NaH (0.080 g, 3.33 mmol) in anhydrous THF (5 mL). Then cyclohexylmethyl 4-bromothiophene-2-carboxylate (0.56 g, 1.847 mmol) was added to the reaction mixture followed by CuI (0.34 g, 1.79 mmol). The reaction mixture was stirred at room temperature for 12 days then aqueous NH4Cl (25%) was added. Aqueous layer was extracted with EtOAc and combined organic layers were washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. Flash chromatography purification (2%-10% EtOAc—hexanes gradient) gave cyclohexylmethyl 4-(cyclohexylmethoxy)thiophene-2-carboxylate as a colorless oil. Yield (0.17 g, 27%); 1H NMR (400 MHz, CD3OD) δ 7.35 (d, J=1.7 Hz, 1H), 6.75 (d, J=1.7 Hz, 1H), 4.07 (d, J=6.3 Hz, 2H), 3.78 (d, J=6.3 Hz, 2H), 1.65-1.90 (m, 12H), 1.15-1.38 (m, 6H), 1.00-1.15 (m, 4H).

1. extractionAqueous layer was extracted with EtOAc
2. washwere washed with brine
3. dry with materialdried over anhydrous MgSO4
4. concentrationconcentrated under reduced pressure
5. customFlash chromatography purification (2%-10% EtOAc—hexanes gradient)