Sodium hydride → 3,4-Dihydro4-(2-dimethylaminoethyl)-6-nitro-2H-1,4-benzoxazine

HRID 424490Notes

Reaction equation

HRID 424490 reaction equation
[N+:1]([C:4]1[CH:13]=[CH:12][C:7]2[O:8][CH2:9][CH2:10][NH:11][C:6]=2[CH:5]=1)([O-:3])=[O:2].[H-].[Na+].Cl.Cl[CH2:18][CH2:19][N:20]([CH3:22])[CH3:21]>CN(C=O)C>[CH3:21][N:20]([CH3:22])[CH2:19][CH2:18][N:11]1[CH2:10][CH2:9][O:8][C:7]2[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 70622256-nitro-3,4-dihydro-2H-1,4-benzoxazineHCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 107771353,4-Dihydro4-(2-dimethylaminoethyl)-6-nitro-2H-1,4-benzoxazineYield 32.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine (1.0 g, 5.55 mmol) in anhydrous DMF (25 mL) under argon was cooled and treated portionwise with sodium hydride (0.677 g, 16.93 mmol) at 5-10° C. 2-chloro-N,N-dimethylethanamine hydrochloride (1.599 g, 11.10 mmol) was added portionwise at 5-10° C., and the resulting heterogeneous red-brown mixture was allowed to warm to room temperature. After 3 hours at room temperature, the mixture was heated to 90° C. and stirred for 30 minutes. The mixture was cooled to room temperature, quenched by the addition of water (25 mL), and diluted with EtOAc. A small amount of 1 N NaOH was added to basify the mixture to pH ˜9-10. The organic layer was separated, and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine (×2), dried (Na2SO4), filtered, and concentrated to afford a dark red oil. The material was purified on silica gel, eluting with 5% MeOH/CH2Cl2, to yield the title compound as a dark orange-red oil (458 mg, 32.8%). 1H NMR (DMSO-d6) δ 7.49-7.39 (m, 2H), 6.87-6.84 (m, 1H), 4.27-4.25 (m, 2H), 3.50-3.37 (m, 4H), 2.43 (t, 2H, J=6.7 Hz), 2.19 (s, 6H); ESI-MS (m/z, %): 252 (MH+, 100).

Workup

  1. temperaturethe mixture was heated to 90° C.
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched by the addition of water (25 mL)
  4. additiondiluted with EtOAc
  5. additionA small amount of 1 N NaOH was added
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was further extracted with EtOAc
  8. washThe combined organic layers were washed with brine (×2)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a dark red oil
  13. customThe material was purified on silica gel
  14. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-93c99f73493644b5a6b9e063bf3604dc
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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