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

HRID 452408Notes

Reaction equation

HRID 452408 reaction equation
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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalyst2×HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a8a4bb0d6e5e4ce194e8231f604d4620
Source dataset
uspto-grants-2013_07
Patent number
US08492372B2

Reaction notes

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