Zifrosilone

Originator

Zifrosilone,Marion Merrell Dow

Uses

Inhibitor (acetylcholinesterase).

Manufacturing Process

3-Trimethylsilyl-bromobenzene:
A mixture of 1,3-dibromobenzene (25.0 g, 106.4 mmol) and trimethylsilylchloride (11.6 g, 106.4 mmol) in diethyl ether (50 ml) was added dropwise in 1.5 hours on magnesium (2.59 g, 106.4 mmol) in diethyl ether (25 ml). Then the mixture was refluxed for 18 hours, cooled to 0°C, treated with 4 N HCl (75 ml). The organic layer was separated, washed with water, brine, dried over MgSO 4 and concentrated. 3-Trimethylsilylbromobenzene was obtained by fractional distillation as a colorless oil (13.4 g, 55% yield, b.p.: 55-62°C/0.8 mmHg.
2,2,2-Trifluoro-1-(3-trimethylsilylphenyl)ethanone:
To a solution of 3-trimethylsilylbromobenzene (7.62 g, 33.3 mmol) in diethyl ether (35 ml) was added 1.5 M n-butyl lithium in hexane (22.2 ml, 33.3 mmol) at 0°C over 10 min. Then the mixture was allowed to react 15 min at room temperature, cooled to -78°C and ethyl trifluoroacetate (14.2 g, 100 mmol) was added over 5 min. Then the mixture was allowed to react 15 min at -78°C, the cooling bath was removed and when the temperature rose to 0°C. 3 N HCl (35 ml) was added dropwise. The organic layer was separated, washed with water, brine, dried over MgSO 4 and concentrated. Chromatography (silica gel, cyclohexane/diethyl ether: 90/10) followed by distillation under reduced pressure afforded the expected compound (zifrosilone) as a colorless oil (4.32 g, 53% yield), boiling point 120°C/0.8 mm Hg; Rf: 0.28 (cyclohexane/diethyl ether: 95/5).

Therapeutic Function

Acetylcholinesterase inhibitor

Raw materials

Preparation Products