反应详情

157 mg of 4-fluorobicyclo[2.2.2]oct-1-ylamine hydrochloride were initially charged in 2 ml of dichloromethane, and then 174 mg of 1,1′-thiocarbonyldiimidazole and 0.172 ml of triethylamine were added. After stirring at room temperature for 30 minutes, the batch was admixed with a mixture of 10 ml of diethyl ether and 10 ml of n-pentane, and washed with water. The organic phase was dried over MgSO4 and concentrated by rotary evaporation, and the residue was dissolved in 1.5 ml of NMP. This solution was added to a suspension of 146 mg of 1-(1-hydroxy-1-methylethyl)cyclopropanesulfonamide and 101 mg of potassium tert-butoxide in 1.5 ml of NMP. After stirring for 1 hour, 149 mg of N-bromosuccinimide were added and the resulting reaction solution was stirred again for 1 hour. The reaction mixture was admixed with 40 ml of water and extracted three times with 15 ml of ethyl acetate. The combined organic phases were washed with 1 N aqueous potassium hydrogensulfate solution and twice with saturated aqueous sodium chloride solution, dried over MgSO4 and concentrated by rotary evaporation. The residue was purified in a purification laboratory by means of preparative HPLC, and the product-containing fractions were lyophilized. This gave the product (9.1 mg) with a molecular weight of 330.4 g/mol (C15H23FN2O3S); MS (ESI): m/e=331 (M+H+).

1. washwashed with water
2. dry with materialThe organic phase was dried over MgSO4
3. concentrationconcentrated by rotary evaporation
4. dissolutionthe residue was dissolved in 1.5 ml of NMP
5. additionThis solution was added to a suspension of 146 mg of 1-(1-hydroxy-1-methylethyl)cyclopropanesulfonamide and 101 mg of potassium tert-butoxide in 1.5 ml of NMP
6. stirringAfter stirring for 1 hour
7. addition149 mg of N-bromosuccinimide were added
8. customthe resulting reaction solution
9. stirringwas stirred again for 1 hour
10. extractionextracted three times with 15 ml of ethyl acetate
11. washThe combined organic phases were washed with 1 N aqueous potassium hydrogensulfate solution and twice with saturated aqueous sodium chloride solution
12. dry with materialdried over MgSO4
13. concentrationconcentrated by rotary evaporation
14. customThe residue was purified in a purification laboratory by means of preparative HPLC