4-bromo-1-chloro-2-methoxybenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Was prepared according to method A with the following variation: A solution of 5-bromo-2-chloroanisol (1.26 g, 5.7 mmol) in THF (7 mL) was added drop-wise to a solution of n-BuLi (1.6 M in hexanes (3.8 mL, 6.1 mmol)) at −78° C. and stirred for 30 min. A solution of 9-oxo-3-aza-spiro[5.5]undecane-3-carboxylic acid tert-butyl ester (475 mg, 1.78 mmol) in THF (7 mL) was added. The mixture was stirred for 1 h. White solid. Mp. 182-185° C. Was prepared The mixture was stirred for 1 h

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 3-necked, 5-L Morton flask equipped with a mechanical stirrer, gas adapter, heating mantle and thermometer was added rac-BINAP (4.24 g, 0.005 equiv) and Pd2(dba)3 (3.20 g, 0.0025 equiv). The flask was evacuated, and back-filled with nitrogen. Toluene (100 mL) was added by cannula. The mixture was stirred at room temperature for 15 min to give a purple solution. Toluene (2.0 L) was then added. 2-Chloro-5-bromoanisole (300.3 g, 1.356 mol, 1 equiv) was added in one portion. Boc-piperazine (252.4 g, 1 equiv) was added in one portion. Sodium tert-butoxide (183.0 g, 1.4 equiv) was added in one portion. The flask was evacuated and back-filled with nitrogen. The mixture was then heated to an internal temperature of 60° C. A heterogeneous light-orange slurry was obtained. After 1 h, the mixture becomes a homogeneous brown solution. After an additional 15 h, the mixture was cooled to room temperature. EtOAc (2.0 L) was added to the stirring mixture. The solid was filtered. The filtrate was washed with EtOAc (100 mL). The combined filtrate was washed with 10% aq. K2CO3 solution (1×1 L), water (1×1 L), and dried over MgSO4. The solvent was removed in vacuo to afford the product as an orange solid (410.3 g, 93% yield). heating mantle and thermometer The flask was evacuated back-filled with nitrogen Toluene (100 mL) was added by cannula to give a purple solution The flask was evacuated back-filled with nitrogen The mixture was then heated to an internal temperature of 60° C A heterogeneous light-orange slurry was obtained After 1 h After an additional 15 h the mixture was cooled to room temperature The solid was filtered The filtrate was washed with EtOAc (100 mL) The combined filtrate was washed with 10% aq. K2CO3 solution (1×1 L), water (1×1 L) dried over MgSO4 The solvent was removed in vacuo