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

HRID 59666Notes

Reaction equation

HRID 59666 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([CH2:12][C:13]1[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]2[C:16]([C@H:17]3[CH2:27][C@H:18]3[CH2:19][O:20]2)=[CH:15][CH:14]=1)(=[O:11])=[O:10].[CH2:28]([N:30]([CH2:47][CH3:48])[CH2:31]/[CH:32]=[CH:33]\[Sn](CCCC)(CCCC)CCCC)[CH3:29].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH2:28]([N:30]([CH2:47][CH3:48])[CH2:31]/[CH:32]=[CH:33]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([CH2:12][C:13]1[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]2[C:16]([C@H:17]3[CH2:27][C@H:18]3[CH2:19][O:20]2)=[CH:15][CH:14]=1)(=[O:11])=[O:10])[CH3:29]

Participants

6

Reactant 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2×HCID 131737060methyl cis-(1aRS,7bSR)-5-(2-bromo-4-fluorobenzenesulfonylmethyl)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 131737059methyl cis-(1aRS,7bSR)-5-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 101.9%

Reagents, catalysts & solvents 2

HCID 76545419Dibenzylideneacetone dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  1. customDMSO (1.6 mL) was degassed
  2. custompurged with nitrogen
  3. temperatureAfter cooling
  4. additionthe mixture was poured into brine
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of methanol and DCM with a gradient of 0-15%

Sources & evidence

ORD record
ord-dc933e5941b0472f9156fe5abfe3a699
Source dataset
uspto-grants-2016_09
Patent number
US09440943B2

Reaction notes

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