background and overview[1]
4-diphenylmagnesium bromide can be used as a pharmaceutical synthesis intermediate. if 4-diphenylmagnesium bromide is inhaled, move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if the eyes are clear in case of contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
preparation[1-2]
the preparation of 4-diphenylmagnesium bromide is as follows:
method 1: add 12.5g 4-bromobiphenyl, 27.38g magnesium, and 50g tetrahydrofuran into the reactor, add 0.125g elemental iodine particles for initiation, add 200g tetrahydrofuran, control the temperature at 40°c, and drop 237.5g 4-bromobiphenyl a mixed solution of benzene and 350g tetrahydrofuran was reacted for 2 hours and then cooled to 4°c to prepare 4-diphenylmagnesium bromide.
method 2: in a 250ml three-necked flask, in a nitrogen atmosphere, add 0.05mol raw material u1 and 0.06mol mg powder, dissolve them in 60ml dry tetrahydrofuran, add 0.0004mol elemental i2, heat to 40°c and stir until the solution turns from yellow it turns colorless. heat the above mixed solution to 80°c and stir for 4 hours. no magnesium powder remains. the reaction is complete and the grignard reagent 4-diphenylmagnesium bromide is generated. no purification is required, and the next step is carried out directly.
apply[1-2]
4-diphenylmagnesium bromide can be used as a pharmaceutical synthesis intermediate. if the following reaction occurs
add 2g cuprous iodide to 4-diphenylmagnesium bromide, continue to cool to -15°c, add dropwise a mixture of 109g (s)-epichloropropane and 109g tetrahydrofuran, and stir for 2.0h to obtain the above compound.
in addition, 4-diphenylmagnesium bromide can also undergo the following reactions
the specific steps are: add 0.03 mol 9-fluorenone to a 250 ml three-necked flask in a nitrogen atmosphere, dissolve it with 40 ml dry tetrahydrofuran, slowly add the above format reagent intermediate v1 solution dropwise, and heat to reflux for 15 hours to generate a large amount of white precipitate was then cooled to room temperature, and saturated nhcl4 was added to convert the grignard salt into alcohol; after the reaction was completed, it was extracted with ether, dried and evaporated, and passed through a silica gel column to obtain a slightly yellow solid tertiary alcohol intermediate w1, hplc purity 99.2% , the yield is 72.5%.
main reference materials
[1] cn201810029965.1 a synthesis method of lcz696 intermediate
[2] cn201710383848.0 an organic compound with fluorene as the core and its application
微信扫一扫打赏
