Diethyl Ether → 4-Fluorobicyclo[2.2.2]octan-1-amine

Participants

Reaction Steps

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+).

Provenance & Evidence