Methyl pyrrole-2-carboxylate → methyl 1-{2-[4-(difluoromethoxy)phenyl]-2-oxoethyl)-1H-pyrrole-2-carboxylate

HRID 1753115Notes

Reaction equation

HRID 1753115 reaction equation
CC(C)([O-])C.[K+].[NH:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12]([O:14][CH3:15])=[O:13].Br[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[CH:22][CH:21]=1)=[O:19]>CN(C=O)C.CCOC(C)=O.O>[F:28][CH:27]([F:29])[O:26][C:23]1[CH:22]=[CH:21][C:20]([C:18](=[O:19])[CH2:17][N:7]2[CH:11]=[CH:10][CH:9]=[C:8]2[C:12]([O:14][CH3:15])=[O:13])=[CH:25][CH:24]=1

Participants

7

Reactant 3

HCID 136930Methyl pyrrole-2-carboxylateHCID 7034962-Bromo-1-(4-(difluoromethoxy)phenyl)ethan-1-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 67366944methyl 1-{2-[4-(difluoromethoxy)phenyl]-2-oxoethyl)-1H-pyrrole-2-carboxylateYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium tert-butoxide (430 mg, 3.82 mmol) was added to a solution of methyl 1H-pyrrole-2-carboxylate (435 mg, 3.48 mmol), and 2-bromo-1-[4-(difluoromethoxy)phenyl]ethanone (1.01 g, 3.82 mmol) in DMF (7.5 mL) at 0° C., the resulting red suspension was stirred from 0° C. to room temperature for 18 h. The reaction mixture was diluted with EtOAc (30 mL) and water (10 mL). The organic layers were then separated and washed with further water (10 mL), dried (MgSO4) filtered and concentrated in vacuo to give an orange residue. The residue was purified by flash column chromatography (Biotage SP4, 40 g cartridge, 10%-20% EtOAc gradient in n-hexanes) to give methyl 1-{2-[4-(difluoromethoxy)phenyl]-2-oxoethyl}-1H-pyrrole-2-carboxylate as a yellow gum, (417 mg, yield 38%). 1H NMR (400 MHz, CDCl3): δ 3.69 (s, 3H), 5.69 (s, 2H), 6.23 (dd, 1H, J 4.0, 2.6 Hz), 6.60 (t, 1H, J 73.0 Hz), 6.82 (dd, 1H, J 2.5, 1.9 Hz), 7.03 (dd, 1H, J 4.0, 1.8 Hz), 7.19 (d, 2H, J 8.8 Hz), 7.97-8.03 (m, 2H).

Workup

  1. customThe organic layers were then separated
  2. washwashed with further water (10 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give an orange residue
  7. customThe residue was purified by flash column chromatography (Biotage SP4, 40 g cartridge, 10%-20% EtOAc gradient in n-hexanes)

Sources & evidence

ORD record
ord-2d85a796e4c34e6fb24099c53d574a03
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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