Bromomethyl 4-methoxyphenyl ketone → HCID 67365424, compound

HRID 1753162Notes

Reaction equation

HRID 1753162 reaction equation
[Br:1][C:2]1[NH:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)=[O:16].[NH4+].[Cl-]>CN(C=O)C>[Br:1][C:2]1[N:6]([CH2:14][C:15]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[O:16])[C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 4965Bromomethyl 4-methoxyphenyl ketoneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 11600885Methyl 5-bromo-1H-pyrrole-2-carboxylate

Product 1

HCID 67365424HCID 67365424, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of methyl 5-bromopyrrole-2-carboxylate (340 mg, 1.7 mmol) in dry DMF (8 mL) was added sodium hydride (60% dispersion in mineral oil, 75 mg, 1.9 mmol) portionwise under nitrogen. After 1 hour at 0° C. a solution of 2-bromo-1-(4-methoxyphenyl)ethanone (500 mg, 2.2 mmol) in DMF (4 mL) was added. The resulting yellow solution was then stirred at room temperature for 2.5 hours. Saturated aqueous solution of NH4Cl (30 mL) was added and the mixture extracted with EtOAc (100 mL). The organic layer was washed with brine (35 mL), dried (MgSO4), filtered and concentrated in vacuo to give a liquid that was purified by flash chromatography (Biotage SP4, 40 g silica cartridge, 0 to 50% EtOAc gradient in hexanes) to give methyl 5-bromo-1-[2-(4-methoxyphenyl)-2-oxoethyl]-1H-pyrrole-2-carboxylate as a white solid (525 mg, yield 88%).

Workup

  1. extractionthe mixture extracted with EtOAc (100 mL)
  2. washThe organic layer was washed with brine (35 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a liquid that
  7. customwas purified by flash chromatography (Biotage SP4, 40 g silica cartridge, 0 to 50% EtOAc gradient in hexanes)

Sources & evidence

ORD record
ord-8a85b85c509247c3a01120dfafec0411
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

Loading…