Preparation of 4-(4-bromophenyl)-4-piperidinol_Industrial additives

Background and overview^[1]

4-(4-Bromophenyl)-4-piperidinol can be used as a pharmaceutical synthesis intermediate. If 4-(4-bromophenyl)-4-piperidinol is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse skin thoroughly with soap and water. If discomfort occurs If you feel sick, seek medical attention; if eye contact occurs, 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.

Structure

Preparation^[1]

1) 3.0 g 4-hydroxy-4-(4-bromophenyl)piperidine and 2.50 g 1-{(3-chloropropyl)carbamoyl-2-oxopyrrolidine in 35 ml DMF The solution was stirred at 105-110°C for 6 hours in the presence of 2.74gNal and 4.22gK2CO3 (reaction condition 1). The reaction mixture was poured into ice water, and the solution was extracted with ethyl acetate. The organic layer was washed with water, dried over MgSO4 and concentrated under reduced pressure. The obtained oily substance was subjected to silica gel column chromatography and eluted with dichloromethane/methanol (15/1-10/1v/v) to obtain 4.20g of the colorless needle-like target compound.

2) Reflex a solution of 2.77g of the above intermediate and 1.60g of p-toluenesulfonic acid in 300ml of toluene for 48 hours to separate water as an azeotropic mixture of toluene. After removal of the solvent, the residue was taken up in ethyl acetate and washed with NaH and water. The solution was dried over Na2SO4 and concentrated under reduced pressure. The oily residue was subjected to silica gel column chromatography and eluted with ethyl acetate-dichloromethane/methanol (20/1v/v) to obtain 2.26g (yield: 89.3%) of the target compound as an oily substance. The maleate salt was recrystallized from i-PrOH to prepare 2.50 g of colorless needles 1-[3-(4-(4-bromophenyl)-1,2,5,6-tetrahydropyridine-1- base)-propyl]-2-oxopyrrolidine. melting point. Melting point 135.5-136.5℃

Amino silicone oil emulsion

Main reference materials

[1] EP0445701 Noveltetrahydropyridinederivatives. Antioxidant 1010