Reacción #7988

Ecuación de reacción

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

Disolventes

acetic acid

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente