Potassium Carbonate → Ethyl 7-methyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

HRID 1465057Notes

Reaction equation

HRID 1465057 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[OH:9].C([O-])([O-])=O.[K+].[K+].Br[CH:17]([CH2:23]Br)[C:18]([O:20][CH2:21][CH3:22])=[O:19]>CC(C)=O>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][CH2:23][CH:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:9][C:3]=2[CH:4]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 760822-Amino-5-methylphenolHCID 97945Ethyl 2,3-dibromopropionate

Product 1

HCID 18788323Ethyl 7-methyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylateYield 47.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 2-amino-5-methylphenol (10 g, 81.3 mmol) in acetone (150 mL) was added K2CO3 (24.5 g, 243.9 mmol) and ethyl 2,3-dibromopropanoate (23.3 g, 89.4 mmol). The mixture was heated at reflux for 16 h. The filtrate was concentrated in vacuo to give an oil. Purification by silica gel chromatography (hexane/ethyl acetate gradient) provided ethyl 7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (8.5 g, 47.3% yield). 1H NMR (400 MHz, CDCl3) δ 6.76 (d, J=0.8 Hz, 1H), 6.60 (dd, J=1.2, 8.0 Hz, 1H), 6.19 (d, J=8.0 Hz, 1H), 4.78 (t, J=3.6 Hz, 1H), 4.29-4.21 (m, 2H), 3.59-3.52 (m, 2H), 2.23 (s, 3H), 1.28 (t, J=7 Hz, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto give an oil
  5. customPurification by silica gel chromatography (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-5a683215ced748de8cf0a61d404dc593
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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