2H-1,4-benzoxazin-3(4H)-one → HCID 63629926, compound

HRID 1483031Notes

Reaction equation

HRID 1483031 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[NH:4][C:3](=[O:11])[CH2:2]1.CC(C)([O-])C.[K+].Br[CH2:19][CH:20]([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23]>CC(N(C)C)=O.CCOCC.O>[CH2:22]([O:21][CH:20]([O:24][CH2:25][CH3:26])[CH2:19][N:4]1[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[O:1][CH2:2][C:3]1=[O:11])[CH3:23]

Participants

7

Reactant 3

HCID 727572H-1,4-benzoxazin-3(4H)-oneHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 23665647Potassium tert-butoxide

Product 1

HCID 63629926HCID 63629926, compoundYield 93.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent

Procedure

Dissolve 2H-1,4-benzoxazin-3(4H)-one (1.0 g, 6.64 mmol) in dimethylacetamide (5 mL); add potassium tert-butoxide (1.54 g, 13.28 mmol); and stir at ambient temperature for 5 minutes. Add 2-bromo-1,1-diethoxyethane (10.1 mL, 66.4 mmol) and tetra-N-butylammonium iodide (2.49 g, 6.64 mmol). Heat the reaction mixture to 80° C. and stir for 2 hours. Thereafter allow the reaction to cool to ambient temperature. Dilute the reaction mixture with Et2O and water; separate the layers; and extract the aqueous layer with additional Et2O. Combine the organic extracts; dry over Na2SO4; filter; and concentrate the filtrate under reduced pressure. Purify via flash column chromatography using a step gradient of 0%, 10%, 20% and 30% of EtOAc in hexanes. Concentrate the desired fractions to afford the title compound (1.65 g, 93.7%) as a waxy solid. 1H (300 MHz, CDCl3): δ 7.36-7.32 (m, 1H), 7.03-6.97 (m, 3H), 4.78 (t, J=5.5 Hz, 1H), 4.59 (s, 2H), 4.02 (d, J=5.5 Hz, 2H), 3.81-3.70 (m, 2H), 3.58-3.48 (m, 2H), 1.16 (t, J=7.0 Hz, 6H).

Workup

  1. temperatureHeat the reaction mixture to 80° C.
  2. stirringstir for 2 hours
  3. customthe reaction
  4. temperatureto cool to ambient temperature
  5. customseparate the layers
  6. extractionand extract the aqueous layer with additional Et2O
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. concentrationand concentrate the filtrate under reduced pressure
  10. customPurify via flash column chromatography
  11. concentrationConcentrate the desired fractions

Sources & evidence

ORD record
ord-b4d30b56c0124535bf9a71f0438f148b
Source dataset
uspto-grants-2016_08
Patent number
US09416138B2

Reaction notes

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