Diethyl azodicarboxylate → Tert-butyl 2-[(2-bromo-5-methoxyphenoxy)methyl]-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 518135Notes

Reaction equation

HRID 518135 reaction equation
[OH:1][CH2:2][CH:3]1[CH:7]=[CH:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[Br:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=1O.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.C1(C)C=CC=CC=1>[Br:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=1[O:1][CH2:2][CH:3]1[CH:7]=[CH:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9]

Participants

6

Reactant 3

HCID 5462977Diethyl azodicarboxylateHCID 11095619tert-butyl 2-(hydroxymethyl)-2,5-dihydro-1H-pyrrole-1-carboxylateHCID 134938392-Bromo-5-methoxyphenol

Product 1

HCID 67325014Tert-butyl 2-[(2-bromo-5-methoxyphenoxy)methyl]-2,5-dihydro-1H-pyrrole-1-carboxylateYield 9.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 2-(hydroxymethyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (8.96 g, 0.45 mol, from Specialty Chemicals, Inc.) and 2-bromo-5-methoxyphenol (9.32 g, 0.46 mol) in THF (180 mL) was added DEAD (20.5 mL) in toluene (40 wt %) dropwise at 0° C. The reaction was stirred for 21 h at RT and the solvent was evaporated. The residue was suspended in methyl tert-butylether (50 mL) and the solution was filtered and concentrated. The resulting residue was dissolved in DCM, washed with 0.6N NaOH (2×25 mL) and the layers were separated. The organic layer was dried with Na2SO4 and the solvent was evaporated. The crude product was purified using an ISCO instrument (330 g RediSep® column), eluting with a gradient of ethyl acetate in heptane (from 0%-20% ethyl acetate over 6 minutes, then 29% ethyl acetate for 20 min) to afford 16.4 g of the title product.

Workup

  1. customthe solvent was evaporated
  2. filtrationthe solution was filtered
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was dissolved in DCM
  5. washwashed with 0.6N NaOH (2×25 mL)
  6. customthe layers were separated
  7. dry with materialThe organic layer was dried with Na2SO4
  8. customthe solvent was evaporated
  9. customThe crude product was purified
  10. washeluting with a gradient of ethyl acetate in heptane (from 0%-20% ethyl acetate over 6 minutes

Sources & evidence

ORD record
ord-d93fb172efa640e883d3eb00bd9bd3ea
Source dataset
uspto-grants-2015_08
Patent number
US09115147B2

Reaction notes

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