Potassium Carbonate → N-{[5-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amine

HRID 452408Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 452408
Br[C:2]1[CH:3]=[C:4]([F:17])[C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH2:13][CH2:14][CH3:15])[O:7][C:6]=2[CH:16]=1.[CH3:18][S:19]([O-:21])=[O:20].[Na+].N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu](I)I.O.CCOC(C)=O>[F:17][C:4]1[C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH2:13][CH2:14][CH3:15])[O:7][C:6]=2[CH:16]=[C:2]([S:19]([CH3:18])(=[O:21])=[O:20])[CH:3]=1

Komponenten

9

Edukt 4

HCID 11430Potassium CarbonateHCID 145742L-Proline2×HCID 2733271Sodium methanesulfinateHCID 44481627N-[(7-bromo-5-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine

Produkt 1

HCID 44481628N-{[5-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amineAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 83717Copper iodideKatalysator2×HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A mixture of N-[(7-bromo-5-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine (0.23 g, 0.76 mmol), sodium methanesulfinate (0.14 g, 1.13 mmol, 85%), copperiodide (14 mg, 0.08 mmol), L-proline (17 mg, 0.15 mmol), potassium carbonate (21 mg, 0.15 mmol) in DMSO (2.5 ml) was degassed with nitrogen. Heating in a microwave oven at 140° C. for 30 min afforded product, but the starting material was not completely converted. Additional copperiodide (14 mg, 0.08 mmol) and L-proline (17 mg, 0.15 mmol) were added and the mixture was heated once again at 140° C. for 30 min. The mixture was brought to ambient temperature and EtOAc (100 ml) and water (50 ml) were added. The phases were separated and the aqueous phase was extracted with EtOAc (3×50 ml). The organic phases were combined, dried (Na2SO4), filtered and evaporated. Purification had to be done three times, by flash column chromatography (EtOAc/MeOH 8:1) before affording the pure title compound (90 mg, 39%). The amine was converted into the hydrochloric acid salt and crystallized from EtOH/DEE (55 mg). M.p. 194° C. 1H-NMR (400 MHz, MeOH): δ 7.36 (2H, m), δ 5.26 (1H, t, J 4.8 Hz), δ 5.05 (2H, dd, J1 20.8 Hz, J2 16.0 Hz), δ 3.13 (3H, s), δ 2.99 (2H, m), δ 2.66 (2H, t, J 7.6 Hz), δ 1.56 (2H, m), δ 0.95 (3H, t, J 7.6 Hz).

Aufarbeitung

  1. customwas degassed with nitrogen
  2. customafforded product
  3. temperaturethe mixture was heated once again at 140° C. for 30 min
  4. customwas brought to ambient temperature
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with EtOAc (3×50 ml)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customPurification

Quellen und Nachweise

ORD-Eintrag
ord-a8a4bb0d6e5e4ce194e8231f604d4620
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08492372B2

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