Acetic Acid → N-{[7-(Methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amine

HRID 452395Notes

Reaction equation

HRID 452395 reaction equation
[CH2:1]([N:8]([CH2:12][CH:13]1[O:18][C:17]2[CH:19]=[C:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH:21]=[CH:22][C:16]=2[CH2:15][O:14]1)CCC)[C:2]1C=CC=C[CH:3]=1.CC(O)=O>[Pd].CCO>[CH3:26][S:23]([C:20]1[CH:21]=[CH:22][C:16]2[CH2:15][O:14][CH:13]([CH2:12][NH:8][CH2:1][CH2:2][CH3:3])[O:18][C:17]=2[CH:19]=1)(=[O:24])=[O:25]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 67155851(+)-N-benzyl-N-{[7-(methylsulfonyl)-4H-1,3-benzodioxin-2-yl]methyl}propan-1-amine

Product 1

HCID 44481357N-{[7-(Methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amineYield 71%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

(−)-N-benzyl-N-{[7-(methylsulfonyl)-4H-1,3-benzodioxin-2-yl]methyl}propan-1-amine (0.25 g, 0.67 mmol), palladium on carbon (10%, 30 mg), concentrated AcOH (0.1 ml) and EtOH (15 ml) was hydrogenated at 40 psi for 1 h. The reaction mixture was filtered through a pad of celite and the filtrate was evaporated to dryness. The crude product was dissolved in EtOAc (100 ml) and basified with Na2CO3 (10%, 50 ml). The layers were separated and the aqueous layer was extracted with EtOAc (2×75 ml). The combined organic layers were collected, dried (Na2SO4), filtered and evaporated to dryness (0.32 g). Purification by flash chromatography (EtOAc/MeOH 10:1) afforded the pure title compound (0.13 g, 71%, >95% e.e.). The amine was converted into the hydrochloric acid salt and crystallized from EtOH/MeOH/DEE. M.p. 235° C. [α]DMeOH=−80°. 1H-NMR (400 MHz, MeOH): δ 7.49 (1H, dd, J1 8.0 Hz J2 2.0 Hz), δ 7.41 (1H, d, 2.0 Hz), δ 7.30 (1H, d, J 8 Hz), δ 5.25 (1H, t, J 5.2 Hz), δ 5.02 (2H, dd, J1 50 Hz, J2 16 Hz), δ 3.1 (3H, s), δ 2.97 (2H, m), δ 2.65 (2H, t, J 7.2 Hz), δ 1.56 (2H, m), δ 0.95 (3H, t, J 7.6 Hz).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of celite
  2. customthe filtrate was evaporated to dryness
  3. dissolutionThe crude product was dissolved in EtOAc (100 ml)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×75 ml)
  6. customThe combined organic layers were collected
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated to dryness (0.32 g)
  10. customPurification by flash chromatography (EtOAc/MeOH 10:1)

Sources & evidence

ORD record
ord-28c4a9eb38f54b558a96d0e756e289be
Source dataset
uspto-grants-2013_07
Patent number
US08492372B2

Reaction notes

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