Water → 4-(3-methoxy-propyl)-2,2-dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one

HRID 1698340Notes

Reaction equation

HRID 1698340 reaction equation
[CH3:1][C:2]1([CH3:16])[C:7](=[O:8])[NH:6][C:5]2[CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[CH:11]=[CH:12][C:4]=2[O:3]1.[CH3:17][O:18][CH2:19][CH2:20][CH2:21]OS(C1C=CC(C)=CC=1)(=O)=O.[H-].[Na+].O>CN(C=O)C>[CH3:17][O:18][CH2:19][CH2:20][CH2:21][N:6]1[C:5]2[CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[CH:11]=[CH:12][C:4]=2[O:3][C:2]([CH3:16])([CH3:1])[C:7]1=[O:8]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 106566312,2-Dimethyl-6-nitro-2H-benzo[B][1,4]oxazin-3(4H)-oneHCID 135229883-Methoxypropyl 4-methylbenzenesulfonate

Product 1

HCID 577907224-(3-methoxy-propyl)-2,2-dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-oneYield 82.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., a solution of 2,2-dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one (35.8 g, 0.161 mol) and 1-methoxy-3-(p-toluenesulfonyloxy)propane (47.6 g, 0.195 mol) in DMF (720 ml) is treated with Kl (5.49 g, 33.1 mmol). After adding 60% of NaH (7.80 g, 0.195 mol) over 10 min, the mixture is stirred at 0° C. for 30 min, warmed to 60° C., stirred for 14 h, and treated with H2O (3500 ml). After the extraction of the mixture with EtOAc (3×400 ml) and Et2O (3×400 ml), the combined org. layer is washed with H2O (2×250 ml), dried (Na2SO4), and evaporated. A SiO2 flash chromatography (2000 g, hexane/EtOAc 5:2) gives 4-(3-methoxy-propyl)-2,2-dimethyl-6-nitro-4H-benzo[1,4]oxazin-3-one (39.0 g, 82%) as yellow oil. Rf (hexane/EtOAc 5:2) 0.45. 1H-NMR (400 MHz, CDCl3) 1.55 (s), 1.91-2.02 (m, 2 H), 3.36 (s), 3.43 (t, J=6.0), 4.07 (t, J=6.0), 7.04 (d, J=9.0), 7.93 (dd, J=9.0, 0.4), 8.09 (d, J=0.4). 13C-NMR (100 MHz, CDCl3) 167.6 (s), 148.9 (s), 143.0 (s), 129.5 (s), 119.8 (d), 117.7 (d), 110.4 (d), 78.9 (s), 69.4 (t), 58.7 (q), 39.7 (t), 27.5 (t), 23.7 (2q).

Workup

  1. temperaturewarmed to 60° C.
  2. stirringstirred for 14 h
  3. extractionAfter the extraction of the mixture with EtOAc (3×400 ml) and Et2O (3×400 ml)
  4. washlayer is washed with H2O (2×250 ml)
  5. dry with materialdried (Na2SO4)
  6. customevaporated

Sources & evidence

ORD record
ord-04fb20dc867d483791a11a0f4320c20e
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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