Ethylene Glycol → Diethyl 6-benzyl-2,3-dihydro-6H-[1,4]dioxino[2,3-c]pyrrole-5,7-dicarboxylate

HRID 1582411Notes

Reaction equation

HRID 1582411 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:8]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:9]([OH:12])[C:10]=1[OH:11])=[O:5])[CH3:2].[CH2:25](O)[CH2:26]O>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:8]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:9]2[O:12][CH2:25][CH2:26][O:11][C:10]=12)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 174Ethylene GlycolHCID 54682554Diethyl 1-benzyl-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate

Product 1

HCID 12990809Diethyl 6-benzyl-2,3-dihydro-6H-[1,4]dioxino[2,3-c]pyrrole-5,7-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

ADC01 (2.9 g, 16.9 mmol) was slowly added to a solution of N-benzyl-3,4-dihydroxypyrrole-2,5-dicarboxylic acid diethyl ester (2.6 g, 7.7 mmol), ethylene glycol (0.5 g, 8.5 mmol), and PH02 (4.4 g, 16.9 mmol) in dry tetrahydrofuran (150 ml) at 0° C. The reaction mixture was allowed to warm to 25° C., stirred for 3 h, and then was refluxed for 21 h. The reaction mixture was then allowed to cool to 25° C. and was concentrated by rotary evaporator to remove the tetrahydrofuran. The residue was diluted with diethyl ether and allowed to stand overnight to enable the tributylphosphine oxide to precipitate out. The tributylphosphine oxide was then removed by filtration and the residue purified by chromatography on silica gel (eluant: ethyl acetate/hexane=3/1) to give 6-benzyl-2, 3-dihydro-6H-[1,4]dioxino[2,3-c]pyrrole-5,7-dicarboxylic acid diethyl ester as a colourless solid in 2.3 g (85%) yield as characterized by 1H NMR, 13C NMR, HRMS, and elemental analysis.

Workup

  1. temperaturewas refluxed for 21 h
  2. temperatureto cool to 25° C.
  3. concentrationwas concentrated by rotary evaporator
  4. customto remove the tetrahydrofuran
  5. additionThe residue was diluted with diethyl ether
  6. waitto stand overnight
  7. customto precipitate out
  8. customThe tributylphosphine oxide was then removed by filtration
  9. customthe residue purified by chromatography on silica gel (eluant: ethyl acetate/hexane=3/1)

Sources & evidence

ORD record
ord-58c87625a019411d98b05808dfb69ba6
Source dataset
uspto-grants-2004_05
Patent number
US06734312B2

Reaction notes

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