1,2-Dibromoethane → methyl 3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

HRID 1660779Notes

Reaction equation

HRID 1660779 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([NH2:11])[CH:5]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:20][CH2:21]Br>CN(C)C=O>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[O:10][CH2:21][CH2:20][NH:11][C:6]=2[CH:5]=1)=[O:12]

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 10815Methyl 3-amino-4-hydroxybenzoateHCID 11430Potassium Carbonate

Product 1

HCID 16244461methyl 3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-amino-4-hydroxy-benzoic acid methyl ester (4.2 g, 25.4 mmol) in dimethylformamide (85 mL) was treated with K2CO3 (14.2 g, 102.9 mmol, 4 equiv.) and 1,2-dibromoethane (19.3 g, 102.9 mmol, 4 equiv.). The mixture was stirred at 70° C. overnight, then filtered to remove the solids. The filtrate was removed under vacuo, and the residue was purified by flash chromatography (heptane/ethyl acetate gradient) to yield 3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid methyl ester, 3.65 g (73%) as a light yellow solid, MS (ISP): m/e=235.1 (M+CH3CN+.); δH (300 MHz; CDCl3) 7.36 (1H, dd, J=8.5, 2.0), 7.30 (1H, d, J=2.0), 6.78 (1H, d, J=8.5), 4.30 (2H, m); 3.85 (3H, s), 3.43 (2H, m).

Workup

  1. filtrationfiltered
  2. customto remove the solids
  3. customThe filtrate was removed under vacuo
  4. customthe residue was purified by flash chromatography (heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-66980f4e5e84451e9c5c214c0962986d
Source dataset
uspto-grants-2011_10
Patent number
US08030308B2

Reaction notes

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