Potassium Carbonate → 1-tert-butyl 2-methyl 3-phenyl-1H-pyrrole-1,2-dicarboxylate

HRID 1478397

Reaction equation

HRID 1478397 reaction equation
Br[C:2]1[CH:6]=[CH:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C:3]=1[C:14]([O:16][CH3:17])=[O:15].C(=O)([O-])[O-].[K+].[K+].[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1(C)C=CC=CC=1.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:24]1([C:2]2[CH:6]=[CH:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C:3]=2[C:14]([O:16][CH3:17])=[O:15])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 441898031-tert-butyl 2-methyl 3-bromo-1H-pyrrole-1,2-dicarboxylate

Product 1

HCID 903861371-tert-butyl 2-methyl 3-phenyl-1H-pyrrole-1,2-dicarboxylateYield 65.9%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 1-tert-butyl 2-methyl 3-bromo-1H-pyrrole-1,2-dicarboxylate (17.6 g, 57.9 mmol) in toluene (200 mL) and water (200 mL) was added potassium carbonate (64.0 g, 463 mmol), followed by phenylboronic acid (10.6 g, 87.0 mmol) and tetrabutylammonium bromide (1.68 g, 5.21 mmol). The reaction mixture degassed for 10 min with nitrogen and then tetrakis(triphenylphosphine)palladium (1.34 g, 1.16 mmol) was added. The resulting slurry was degassed with nitrogen for 30 min and then heated to reflux for 16 h. The reaction mixture was concentrated under reduced pressure to remove water and toluene. Water was then added to the residue and the mixture extracted by ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using CombiFlash (REDISEP®, silica gel, 80 g, 20% EtOAc/hexanes) to obtain 1-tert-butyl 2-methyl 3-phenyl-1H-pyrrole-1,2-dicarboxylate (11.5 g, 65.9%) as a tan solid. 1H NMR (400 MHz, CD3OD) δ ppm: 1.60 (s, 9H), 3.79 (s, 3H), 6.40 (d, J=3.4 Hz, 1H), 7.37 (m, 6H).

Workup

  1. customThe reaction mixture degassed for 10 min with nitrogen
  2. customThe resulting slurry was degassed with nitrogen for 30 min
  3. temperatureheated
  4. temperatureto reflux for 16 h
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. customto remove water and toluene
  7. additionWater was then added to the residue
  8. extractionthe mixture extracted by ethyl acetate
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d0cc616d177942f88b47f003bb49788b
Source dataset
uspto-grants-2016_08
Patent number
US09403834B2

Linked notes

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