Reaction #7936

Reaction equation

9a-butyl-4-(4-hydroxyphenyl)-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one

cesium carbonate

1-(2-chloroethyl)-piperidine monohydrochloride

→

9a-butyl-7-methoxy-4-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Yield 96.3%

Solvents

acetone

EtOAc

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Filtrationfiltered
3. 3
   Otherto remove salts
4. 4
   WashThe filtrate was washed with water and brine
5. 5
   Dryingdried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated under vacuum to a yellow gum (0.95 g)
8. 8
   OtherThe crude product was purified by chromatography on EM silica gel 60 (230-400 mesh, 50 mL dry)
9. 9
   Washas eluting solvent
10. 10
    workup.ADDITIONThe product containing fractions
11. 11
    Otherwere evaporated under vacuum

Procedure

A mixture of crude 9a-butyl-4-(4-hydroxyphenyl)-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one (787 mg, approx. 2 mmol), cesium carbonate (1.564 g, 4.8 mmol), and 1-(2-chloroethyl)-piperidine monohydrochloride (442 mg, 2.4 mmol) in acetone (5 mL) was stirred and heated in an oil bath at 60° C. for 4 hours. After cooling to room temperature, the mixture was diluted with EtOAc and filtered to remove salts. The filtrate was washed with water and brine, dried over MgSO4, filtered, and evaporated under vacuum to a yellow gum (0.95 g). The crude product was purified by chromatography on EM silica gel 60 (230-400 mesh, 50 mL dry) using 2% MeOH+1% Et3N in EtOAc as eluting solvent. The product containing fractions were evaporated under vacuum and the residue stripped with toluene to provide 9a-butyl-7-methoxy-4-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1,2,9,9a-tetrahydro-3H-fluoren-3-one (912 mg, 96% weight pure) as a pale yellow gum.

Source