Water → 2-Amino-3-methoxy-4-(3-morpholin-4-ylpropoxy)benzonitrile

HRID 536229Notes

Reaction equation

HRID 536229 reaction equation
[CH3:1][O:2][C:3]1[C:4]([N+:21]([O-])=O)=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[C:6]#[N:7].O>C(O)(=O)C.[Fe]>[NH2:21][C:4]1[C:3]([O:2][CH3:1])=[C:10]([O:11][CH2:12][CH2:13][CH2:14][N:15]2[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]

Participants

5

Reactant 2

HCID 962WaterHCID 582198483-Methoxy-4-(3-morpholin-4-ylpropoxy)-2-nitrobenzonitrile

Product 1

HCID 582198372-Amino-3-methoxy-4-(3-morpholin-4-ylpropoxy)benzonitrileYield 92.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

3-Methoxy-4-(3-morpholin-4-ylpropoxy)-2-nitrobenzonitrile (Step 2, 7.7 g, 24.1 mmol) was suspended in acetic acid (170 mL) and cooled to 0° C. Water (0.4 mL) was added, followed by iron powder (6.7 g, 120 mmol) and the resulting mixture was stirred at room temperature for 4 h at which time the reaction mixture was filtered through a pad of Celite and washed with acetic acid (400 mL). The filtrate was concentrated under reduced pressure to 100 mL and diluted with EtOAc (200 mL) at which time potassium carbonate was added slowly. The resulting slurry was filtered through a pad of Celite washing with EtOAc and water. The layers were separated and the organic layer was washed with saturated sodium bicarbonate solution. The organic layer was separated and passed through a pad of silica gel. The resultant solution was concentrated under reduced pressure to provide the title compound (6.5 g, 92%): 1H NMR (DMSO-d6) δ: 7.13 (1H, d), 6.38 (1H, d), 5.63 (2H, br s), 4.04 (2H, t), 3.65 (3H, s), 3.55 (4H, m), 2.41 (2H, t), 2.38 (4H, m), 1.88 (2H, m).

Workup

  1. filtrationwas filtered through a pad of Celite
  2. washwashed with acetic acid (400 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure to 100 mL
  4. additiondiluted with EtOAc (200 mL) at which time potassium carbonate
  5. additionwas added slowly
  6. filtrationThe resulting slurry was filtered through a pad of Celite
  7. washwashing with EtOAc and water
  8. customThe layers were separated
  9. washthe organic layer was washed with saturated sodium bicarbonate solution
  10. customThe organic layer was separated
  11. concentrationThe resultant solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1f7ae79918d24b9582b61dba73cdbf46
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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