4-bromo-N,N-dimethylaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (2.5 M in hexanes, 51 mL, 127 mmol) was added dropwise to 4-bromo-N,N-dimethylaniline (23.1 g, 115 mmol, Aldrich Chemical Co.) in anhydrous THF at -78° C. After 10 min. a solution of N-methyl-N-methoxyheptanamide (10.0 g, 57.7 mmol) in 20 mL THF was added dropwise via canula. The reaction was allowed to proceed 1 hr., then quenched with 1 N aq. HCl and carefully poured into sat. NaHCO3. The aqueous layer was extracted with ethyl ether, and the combined organic fraction was washed with water, brine, dried (MgSO4), and concentrated in vacuo. Flash chromatography (15% EtOAc/hexanes) yielded 1-(4-dimethylaminophenyl)heptan-1-one as a yellow solid (6.49 g, 48%). MS 234 (M+H)+. , then quenched with 1 N aq. HCl carefully poured into sat. NaHCO3 The aqueous layer was extracted with ethyl ether the combined organic fraction was washed with water, brine dried (MgSO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4.0 g of 4-bromo-N,N-dimethylaniline in 50 ml of dry tetrahydrofuran at -78° C. was treated with 23.5 ml of 1.7M tert-butyllithium in pentane under nitrogen over 5 minutes with rapid stirring. After 0.5 hour, the slurry was warmed to -30° C. and added to a solution of 4.0 g of α,α-difluorophenylacetate in 50 ml of dry tetrahydrofuran at -78° C. After 1 hour at -78° C., the solution was allowed to warm to room temperature and stirred overnight. The solution was poured into water and extracted with ethyl acetate. Evaporation left a solid which was purified by flash chromatography (1:1 ethyl acetate-hexane) to give a powder. Recrystallization from ethyl acetate-hexane gave 1.75 g of 2,2-difluoro-1-[4-(dimethylamino)phenyl]-2-phenylethanone, m.p. 115°-116° C. After 1 hour at -78° C. to warm to room temperature extracted with ethyl acetate Evaporation left a solid which was purified by flash chromatography (1:1 ethyl acetate-hexane) to give a powder Recrystallization from ethyl acetate-hexane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (124 mg, 5.1 mmol) is covered with 1 ml of distilled THF and heated at 60° C. with stirring. A solution of 4-bromo-N,N-dimethylaniline (1.02 g, 5.1 mmol) in 5 ml of distilled THF is added dropwise over the course of 20 min. The reaction mixture is heated at reflux of the THF for 1 h. A solution of 5,6-di(tert-butyldimethylsilyloxy)indan-1-one (2 g, 5.1 mmol) in 10 ml of distilled THF is added dropwise at room temperature over the course of 5 min to this yellow-green solution. The mixture is brought to reflux for 20 h. The reaction mixture, which is violet in colour, is hydrolyzed by saturated aqueous ammonium chloride solution, then extracted with ethyl acetate. The organic phase is washed with saturated aqueous NaCl solution, then dried over MgSO4. The solvent is evaporated under reduced pressure. The desired product is purified by chromatography with an eluent: 9:1 hexane/ethyl acetate, and is obtained in the form of an oil (0.9 g; 36%) The reaction mixture is heated to reflux for 20 h extracted with ethyl acetate The organic phase is washed with saturated aqueous NaCl solution dried over MgSO4 The solvent is evaporated under reduced pressure The desired product is purified by chromatography with an eluent 9:1 hexane/ethyl acetate, and is obtained in the form of an oil (0.9 g; 36%)