反应详情

温度

134 °C

3-Iodo-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid methoxy-methyl-amide (18 g, 47 mmol), CuI (14.5 g, 76 mmol) and KF (4.4 g, 76 mmol) are dissolved in DMF (80 mL). The solution is heated to 134° C. and methyl chlorodifluoroacetate (16.26 g, 113 mmol) is added via syringe pump over a period of 4 h. Gas evolution is observed. Upon complete addition, the mixture is cooled and poured into water/ice. The precipitate that forms is collected, suspended in DCM (600 mL), and filtered through a celite pad. The filtrate is washed with 0.5 N aq. HCl (250 mL), followed by sat. aq. NaHCO3 solution, dried over Na2SO4, filtered and evaporated to give 5,5-dimethyl-3-trifluoromethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid methoxy-methyl-amide (14 g) as a brown oil; LC-MS: tR=1.10 min, [M+1]=322.20.

1. additionUpon complete addition
2. temperaturethe mixture is cooled
3. customThe precipitate that forms is collected
4. filtrationfiltered through a celite pad
5. washThe filtrate is washed with 0.5 N aq. HCl (250 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customevaporated