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

HRID 7840

Reaction equation

HRID 7840 reaction equation
[CH2:1]([C:5]12[CH2:17][CH2:16][C:15](=[O:18])[C:14]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([O:26][CH3:27])=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>CC(C)=O.CCOC(C)=O>[CH2:1]([C:5]12[CH2:17][CH2:16][C:15](=[O:18])[C:14]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:36][CH2:37][N:38]4[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]4)=[CH:21][CH:20]=3)=[C:13]1[C:12]1[C:7](=[CH:8][C:9]([O:26][CH3:27])=[CH:10][CH:11]=1)[CH2:6]2)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 219909159a-butyl-4-(4-hydroxyphenyl)-7-methoxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Product 1

HCID 219909249a-butyl-7-methoxy-4-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1,2,9,9a-tetrahydro-3H-fluoren-3-oneYield 96.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

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.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered
  3. customto remove salts
  4. washThe filtrate was washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under vacuum to a yellow gum (0.95 g)
  8. customThe crude product was purified by chromatography on EM silica gel 60 (230-400 mesh, 50 mL dry)
  9. washas eluting solvent
  10. additionThe product containing fractions
  11. customwere evaporated under vacuum

Sources & evidence

ORD record
ord-1a4333548b494637b07c329108b8dcf4
Source dataset
uspto-grants-2006_08
Patent number
US07087599B2

Linked notes

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