Reaktion #7988

Reaktionsgleichung

2-butyl-6-fluoro-5-methoxy-4-methyl-2-(3-oxohexyl)-1-indanone

1,8-diazabicyclo[5.4.0]undec-7-ene

2-butyl-6-fluoro-5-methoxy-4-methyl-1-indanone

propyl vinyl ketone

HCl

→

9a-butyl-4-ethyl-6-fluoro-7-methoxy-8-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one

Lösungsmittel

acetic acid

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was evaporated under vacuum
2. 2
   Sonstigeto give a residue
3. 3
   workup.STIRRINGstirred
4. 4
   Temperaturwhile heating in an 80° C. oil bath for 6 hours
5. 5
   TemperaturAfter cooling
6. 6
   Sonstigethe mixture was partitioned between EtOAc (25 mL) and saturated aqueous K2CO3 (25 mL)
7. 7
   WaschenThe organic phase was washed with brine (10 mL)
8. 8
   Trocknendried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated under vacuum to an oil (138 mg)
11. 11
    SonstigeThe crude product was purified by preparative layer chromatography on two 0.1×20×20 cm silica gel GF plates
12. 12
    WaschenThe product bands were eluted with EtOAc
13. 13
    Sonstigethe eluent evaporated under vacuum

Vorschrift

A solution of 2-butyl-6-fluoro-5-methoxy-4-methyl-1-indanone (118 mg, 0.47 mmol) in anhydrous tetrahydrofuran (0.47 mL) was treated with propyl vinyl ketone (0.065 mL, 0.56 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.0143 mL, 0.094 mmol). The mixture was stirred and heated in an oil bath at 50° C. for 6 hours and then at room temperature for 64 hours. The solvent was evaporated under vacuum to give a residue consisting mainly of 2-butyl-6-fluoro-5-methoxy-4-methyl-2-(3-oxohexyl)-1-indanone. This material was dissolved in acetic acid (2 mL), treated with aqueous 6N HCl (1.5 mL), and stirred while heating in an 80° C. oil bath for 6 hours. After cooling, the mixture was partitioned between EtOAc (25 mL) and saturated aqueous K2CO3 (25 mL). The organic phase was washed with brine (10 mL), dried over MgSO4, filtered, and evaporated under vacuum to an oil (138 mg). The crude product was purified by preparative layer chromatography on two 0.1×20×20 cm silica gel GF plates, developing with CH2Cl2. The product bands were eluted with EtOAc and the eluent evaporated under vacuum to afford 9a-butyl-4-ethyl-6-fluoro-7-methoxy-8-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (93 mg) as an oil.

Quelle