Ammonium Chloride → 6-amino-4-(3-methoxy-propyl)-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one

HRID 1698341Notes

Reaction equation

HRID 1698341 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]2[CH:12]=[C:13]([N+:16]([O-])=O)[CH:14]=[CH:15][C:10]=2[O:9][C:8]([CH3:20])([CH3:19])[C:7]1=[O:21].[NH4+].[Cl-]>[Zn].O>[NH2:16][C:13]1[CH:14]=[CH:15][C:10]2[O:9][C:8]([CH3:20])([CH3:19])[C:7](=[O:21])[N:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:11]=2[CH:12]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 577907224-(3-methoxy-propyl)-2,2-dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 577911746-amino-4-(3-methoxy-propyl)-2,2-dimethyl-4H-benzo[1,4]oxazin-3-oneYield 105.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

At room temperature, an ethanolic solution (80 ml) of 4-(3-methoxy-propyl)-2,2-dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one (9.76 g, 33.2 mmol) is treated with H2O (80 ml), NH4Cl (3.58 g, 66.9 mmol), and powdered Zn (10.97 g, 0.17 mol), heated to 80° C., stirred for 2 h under reflux, cooled to room temperature, and filtered via celite pad. After washing the cake with CH2Cl2 for several times, the both layers of the combined filtrate are separated. The aq. layer is treated with 5N NaOH (6.0 ml) to adjust its pH 9˜10, and extracted with CH2Cl2 (3×100 ml). The combined org. layer is washed with sat. aqueous solution of NaHCO3 (100 ml) and brine (50 ml), dried (Na2SO4), and evaporated. A SiO2 flash chromatography (250 g, CH2Cl2/acetone 3:1) gives 6-amino-4-(3-methoxy-propyl)-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one (9.23 g, 99%) as brown oil. Rf(CH2Cl2/EtOAc 2:1) 0.34. 1H-NMR (400 MHz, CDCl3) 1.39 (s), 1.80-1.91 (m, 2 H), 3.28 (s), 3.35 (t, J=8.0), 3.44 (br. s), 3.88 (t, J=9.0), 6.23 (dd, J=9.0, 0.4), 6.33 (d, J=0.4), 6.68 (d, J=9.0).

Workup

  1. temperatureunder reflux
  2. temperaturecooled to room temperature
  3. filtrationfiltered via celite pad
  4. washAfter washing the cake with CH2Cl2 for several times
  5. customthe both layers of the combined filtrate are separated
  6. additionThe aq. layer is treated with 5N NaOH (6.0 ml)
  7. extractionextracted with CH2Cl2 (3×100 ml)
  8. washlayer is washed with sat. aqueous solution of NaHCO3 (100 ml) and brine (50 ml)
  9. dry with materialdried (Na2SO4)
  10. customevaporated

Sources & evidence

ORD record
ord-acb0e62b175c4932a68edb0622d7560e
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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