Hydrochloric Acid → 2-Amino-4-(benzyloxy)-5-methoxybenzonitrile

HRID 749152Notes

Reaction equation

HRID 749152 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([N+:17]([O-])=O)[C:12]([C:13]#[N:14])=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl.O1CCOCC1>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)C.ClCCl.O>[NH2:17][C:15]1[CH:16]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:10]([O:20][CH3:21])=[CH:11][C:12]=1[C:13]#[N:14]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 24489Sodium DithioniteHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 116736184-(Benzyloxy)-5-methoxy-2-nitrobenzonitrile

Product 1

HCID 117015842-Amino-4-(benzyloxy)-5-methoxybenzonitrileYield 82.5%

Reagents, catalysts & solvents 4

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 4-benzyloxy-3-methoxy-6-nitrobenzonitrile (46 g, 162 mmol), sodium bicarbonate (95 g, 1.13 mol), water (750 ml), dichloromethane (550 ml) and tetrabutylammonium chloride (30 g, 108 mmol) was rapidly stirred at 20° C. and treated portionwise with sodium dithionite (66 g, 379 mmol) over 2 hours. The mixture was stirred for a further 1 hour then the phases separated. The aqueous phase was extracted with dichloromethane (2×200 ml) and the combined organic solution washed with water (300 ml) and dried over magnesium sulphate. The solution was concentrated to 250 ml and 4.0 N hydrochloric acid in 1,4-dioxane (150 ml, 0.6 mol) added. The reaction was then diluted with diethyl ether (1000 ml) and cooled on ice. The resulting solid was collected by suction filtration and washed with diethyl ether. The solid was stirred in methanol (1000 ml) and sodium bicarbonate solution (800 ml) added (pH 8) and the mixture stirred for 1 hour. The solid was collected by suction filtration, washed with water, methanol and dried in vacuo to yield 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (34 g, 82% yield) as light brown solid:

Workup

  1. stirringThe mixture was stirred for a further 1 hour
  2. customthe phases separated
  3. extractionThe aqueous phase was extracted with dichloromethane (2×200 ml)
  4. washthe combined organic solution washed with water (300 ml)
  5. dry with materialdried over magnesium sulphate
  6. additionadded
  7. temperaturecooled on ice
  8. filtrationThe resulting solid was collected by suction filtration
  9. washwashed with diethyl ether
  10. stirringThe solid was stirred in methanol (1000 ml)
  11. additionsodium bicarbonate solution (800 ml) added (pH 8)
  12. stirringthe mixture stirred for 1 hour
  13. filtrationThe solid was collected by suction filtration
  14. washwashed with water, methanol
  15. customdried in vacuo

Sources & evidence

ORD record
ord-cdf271c5f45b49d5bb90560b6977d1f6
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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