Boron trifluoride etherate → (R)-N-(2-(5-Bromo-2-fluorophenyl)-1-((2-cyanopropan-2-yl)sulfonyl)-3-fluoropropan-2-yl)-2-methylpropane-2-sulfinamide

HRID 627637

Reaktionsgleichung

Reaktionsgleichung von HRID 627637
[CH3:1][C:2]([S:6]([CH3:9])(=[O:8])=[O:7])([CH3:5])[C:3]#[N:4].C([Li])CCC.[Br:15][C:16]1[CH:17]=[CH:18][C:19]([F:32])=[C:20](/[C:22](=[N:25]/[S@@:26]([C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])/[CH2:23][F:24])[CH:21]=1.B(F)(F)F.CCOCC>C1COCC1>[Br:15][C:16]1[CH:17]=[CH:18][C:19]([F:32])=[C:20]([C:22]([NH:25][S@@:26]([C:28]([CH3:30])([CH3:29])[CH3:31])=[O:27])([CH2:23][F:24])[CH2:9][S:6]([C:2]([C:3]#[N:4])([CH3:5])[CH3:1])(=[O:8])=[O:7])[CH:21]=1

Komponenten

6

Edukt 4

HCID 8000Boron trifluoride etherateHCID 3014848Propanenitrile, 2-methyl-2-(methylsulfonyl)-HCID 90301236(NZ,R)-N-[1-(5-bromo-2-fluorophenyl)-2-fluoroethylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Produkt 1

HCID 86715719(R)-N-(2-(5-Bromo-2-fluorophenyl)-1-((2-cyanopropan-2-yl)sulfonyl)-3-fluoropropan-2-yl)-2-methylpropane-2-sulfinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 2-methyl-2-(methylsulfonyl)propanenitrile (1.654 g, 11.24 mmol) in THF (14 mL) at −78° C. was added a 2.5 M solution of n-butyllithium in hexanes (4.49 mL, 11.24 mmol) dropwise via syringe. After 30 minutes at −78° C., a 0° C. solution of (R,Z)—N-(1-(5-bromo-2-fluorophenyl)-2-fluoroethylidene)-2-methylpropane-2-sulfinamide (1.9 g, 5.62 mmol) in THF (14.00 mL), which had been pretreated with boron trifluoride diethyl etherate (0.693 mL, 5.62 mmol) at 0° C. for 15 minutes, was added dropwise via cannula. The reaction was stirred for 2 hours at −78° C., and then quenched with saturated aqueous ammonium chloride at −78° C. and diluted with water and ethyl acetate. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with water and saturated aqueous sodium chloride, and dried over sodium sulfate. The solution was filtered, concentrated, and purified by silica-gel chromatography, eluting with 25% ethyl acetate in hexanes followed by 40% ethyl acetate hexane to provide the title compound. The product was isolated as a 2:1 mixture of diastereomers. LC/MS (ESI+) m/z=485, 487 (M+H; 2 bromine isotopes).

Aufarbeitung

  1. additionwas added dropwise via cannula
  2. customquenched with saturated aqueous ammonium chloride at −78° C.
  3. additiondiluted with water and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic extracts were washed with water and saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulfate
  8. filtrationThe solution was filtered
  9. concentrationconcentrated
  10. custompurified by silica-gel chromatography
  11. washeluting with 25% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-4a95a3c3b16549b4ac16428989764937
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309263B2

Verknüpfte Notizen

Wird geladen…