Tri-tert-butylphosphine tetrafluoroborate → methyl (1aRS,7bSR)-5-(N-{2-[(Z)-3-(tert-butyldimethylsilanyloxy)-2-methylprop-1-enyl]-4-fluorobenzenesulfonyl]-N-methoxycarbonyl-amino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 928061Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 928061
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([N:12]([C:17]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]2[C:20]([CH:21]3[CH2:31][CH:22]3[CH2:23][O:24]2)=[CH:19][CH:18]=1)[C:13]([O:15][CH3:16])=[O:14])(=[O:11])=[O:10].[C:32]([Si:36]([CH3:56])([CH3:55])[O:37][CH2:38]/[C:39](/[CH3:54])=[CH:40]\[Sn](CCCC)(CCCC)CCCC)([CH3:35])([CH3:34])[CH3:33].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCOCC1.CS(C)=O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:36]([O:37][CH2:38]/[C:39](/[CH3:54])=[CH:40]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([N:12]([C:17]1[C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]2[C:20]([CH:21]3[CH2:31][CH:22]3[CH2:23][O:24]2)=[CH:19][CH:18]=1)[C:13]([O:15][CH3:16])=[O:14])(=[O:11])=[O:10])([C:32]([CH3:33])([CH3:34])[CH3:35])([CH3:55])[CH3:56]

Komponenten

8

Edukt 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborate2×HCID 11351986tert-butyl-dimethyl-((Z)-2-methyl-3-tributylstannanylallyloxy)silaneHCID 77979724methyl (1aRS,7bSR)-5-[N-(2-bromo-4-fluorobenzenesulfonyl)-N-(methoxycarbonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate2×

Produkt 1

HCID 86713360methyl (1aRS,7bSR)-5-(N-{2-[(Z)-3-(tert-butyldimethylsilanyloxy)-2-methylprop-1-enyl]-4-fluorobenzenesulfonyl]-N-methoxycarbonyl-amino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateAusbeute 74,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator2×HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of methyl (1aRS,7bSR)-5-[N-(2-bromo-4-fluorobenzenesulfonyl)-N-(methoxy-carbonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 65, 0.257 g), tert-butyl-dimethyl-((Z)-2-methyl-3-tributylstannanylallyloxy)silane (0.475 g), tris(dibenzylideneacetone)dipalladium(0) (0.023 g) and tri-tert-butylphosphonium tetrafluoroborate (0.015 g) in dioxane (8 mL) and DMSO (0.8 mL) was stirred and heated at 90° C. under nitrogen for 1 hour. Further tris(dibenzylideneacetone)dipalladium(0) (0.023 g) and tri-tert-butylphosphonium tetrafluoroborate (0.015 g) were added and heating was continued for a further 40 minutes. After cooling, the mixture was diluted with ethyl acetate, washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-20% to give methyl (1aRS,7bSR)-5-(N-{2[(Z)-3-(tert-butyldimethylsilanyloxy)-2-methylprop-1-enyl]-4-fluorobenzenesulfonyl]-N-methoxycarbonyl-amino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.231 g) as a colourless gum.

Aufarbeitung

  1. temperatureheating
  2. temperatureAfter cooling
  3. washwashed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-20%

Quellen und Nachweise

ORD-Eintrag
ord-6ec2a7cdb2664cd99f5fde0284c44638
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290472B2

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