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

HRID 536213Notes

Reaction equation

HRID 536213 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 (Step 5, 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 the title compound (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-c6c6afeffd70414688a1d38d563bbe29
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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