Ethylenediamine → 3-(benzyloxy)-6-(4,5-dihydro-1H-imidazol-2-yl)-2-methoxyaniline

HRID 339763Notes

Reaction equation

HRID 339763 reaction equation
[NH2:1][C:2]1[C:9]([O:10][CH3:11])=[C:8]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[S].[CH2:21](N)[CH2:22][NH2:23]>>[CH2:13]([O:12][C:8]1[C:9]([O:10][CH3:11])=[C:2]([C:3]([C:4]2[NH:23][CH2:22][CH2:21][N:5]=2)=[CH:6][CH:7]=1)[NH2:1])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 3

HCID 3301EthylenediamineHCID 5362487SulfurHCID 582198492-Amino-4-(benzyloxy)-3-methoxybenzonitrile

Product 1

HCID 70592683-(benzyloxy)-6-(4,5-dihydro-1H-imidazol-2-yl)-2-methoxyanilineYield 86%

Conditions

Temperature
100 °C

Procedure

A mixture of 2-amino-4-(benzyloxy)-3-methoxybenzonitrile (144 g, 566 mmol) and sulfur (55 g, 1.7 mol) in ethylenediamine (800 mL) was degassed for 30 minutes then heated to 100° C. After 16 h the reaction mixture was cooled to room temperature and then filtered. The filtrate was concentrated under reduced pressure, diluted with a saturated sodium bicarbonate solution and extracted with EtOAc. The organic layer was washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The resulting solids were recrystallized from EtOAc and hexanes to afford 3-(benzyloxy)-6-(4,5-dihydro-1H-imidazol-2-yl)-2-methoxyaniline (145 g, 86%): 1H NMR (DMSO-d6) δ: 7.27-7.48 (5H, m), 7.14 (1H, d), 6.92 (2H, m), 6.64 (1H, m), 6.32 (1H, d), 5.11 (2H, s), 3.67 (3H, s), 3.33 (2H, s).

Workup

  1. customwas degassed for 30 minutes
  2. temperatureAfter 16 h the reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. additiondiluted with a saturated sodium bicarbonate solution
  6. extractionextracted with EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting solids were recrystallized from EtOAc and hexanes

Sources & evidence

ORD record
ord-2830c86b09bc436e857003d7fbd58c89
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

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