Reacción #87944

Ecuación de reacción

methyl cis-(1aRS,7bSR)-5-(2-bromo-4-fluorobenzenesulfonylmethyl)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

Intermediate 5

methyl cis-(1aRS,7bSR)-5-(2-bromo-4-fluorobenzenesulfonylmethyl)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)amine

Intermediate 2

N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)amine

tri-tert-butylphosphonium tetrafluoroborate

→

methyl cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

Rendimiento 101.9%

Disolventes

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroDMSO (1.6 mL) was degassed
2. 2
   Otropurged with nitrogen
3. 3
   TemperaturaAfter cooling
4. 4
   workup.ADDITIONthe mixture was poured into brine
5. 5
   Extracciónextracted with ethyl acetate
6. 6
   SecadoThe organic layer was dried (MgSO4)
7. 7
   Filtraciónfiltered
8. 8
   OtroThe filtrate was evaporated to dryness
9. 9
   Otrothe residue was purified by chromatography on silica
10. 10
    Lavadoeluting with a mixture of methanol and DCM with a gradient of 0-15%

Procedimiento

A mixture of methyl cis-(1aRS,7bSR)-5-(2-bromo-4-fluorobenzenesulfonylmethyl)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 5, 0.66 g), N,N-diethyl-N—((Z)-1-tributylstannanylprop-1-en-3-yl)amine (Intermediate 2, 1.17 g), tri-tert-butylphosphonium tetrafluoroborate (0.145 g), Iris-(dibenzylideneacetone)-dipalladium (0.066 g) in dioxane (16 mL) and DMSO (1.6 mL) was degassed and purged with nitrogen, then heated at 100° C. for 1.5 hours. After cooling, the mixture was poured into brine and extracted with ethyl acetate. The organic layer was dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-15% to give methyl cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.72 g) as a glass.

Fuente