反应详情

Add n-BuLi (20.2 mL, 1.6M in hexanes, 32.3 mmol) into a solution of 2,2,6,6-tetramethyl-piperidine (4.56 g, 32.6 mmol) in hexanes (30 mL) at −78° C. Add 1-bromo-2-fluoro-benzene (4.71 g, 26.9 mmol) and stir for 1 hr. Slowly add 4-dimethylamino-cyclohexanone (3.80 mL) in hexanes (30 mL) and stir for 1 hr. Remove the cooling bath and stir for two more hours. Partition the reaction mixture between saturated aqueous NaCl and ethyl acetate, dry the organic phase with anhydrous sodium sulfate, evaporate the solvent, and purify the residue by chromatography on a silica gel column (DCM: 2M NH3 in MeOH, gradient) to give the title compound (2.04 g): MS (ES): m/z=318 (M+H)+ and 316 (M−H)−. 1HNMR (CDCl3): δ 7.43 (m, 2H), 6.98 (m, 1H), 2.45 (m, 2H), 2.21 (s, 6H), 2.13 (m, 1H), 1.92 (m, 2H), 1.64 (m, 4H).

1. customRemove the cooling bath
2. customPartition the reaction mixture between saturated aqueous NaCl and ethyl acetate
3. dry with materialdry the organic phase with anhydrous sodium sulfate
4. customevaporate the solvent
5. custompurify the residue by chromatography on a silica gel column (DCM: 2M NH3 in MeOH, gradient)