Methyl chloroformate → methyl 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 1594441Notes

Reaction equation

HRID 1594441 reaction equation
C(N(CC)C(C)C)(C)C.Cl[C:11]([O:13][CH3:14])=[O:12].[F:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[C:23]1[CH2:27][NH:26][CH:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=1>ClCCl>[F:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[C:23]1[CH2:27][N:26]([C:11]([O:13][CH3:14])=[O:12])[CH:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 590017764-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole

Product 1

HCID 10245153methyl 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N,N-Diisopropylethylamine (0.19 mL, 1.1 mmol, 6.0 equiv) and methyl chloroformate (0.014 uL, 0.18 mmol, 1.0 equiv) were added to a solution of 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole (1-5, 0.18 mmol, 1 equiv) in dichloromethane (10 mL) at 23° C., and the resulting mixture was stirred for 1 hour, then concentrated. The residue was partitioned between saturated aqueous sodium bicarbonate solution (40 mL) and ethyl acetate (2×35 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) to provide methyl 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (1-6) as an off-white solid. 1H NMR (500 MHz, CD3OD) one rotamer: δ 7.32 (m, 3H), 7.25 (m, 2H), 7.20 (m, 1H), 7.16 (m, 1H), 7.07 (m, 1H), 6.38 (br s, 1H), 5.67 (m, 1H), 4.74 (br s, 2H), 3.70 (s, 3H). LRMS m/z (M+H) 316.0 found, 316.1 required.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (40 mL) and ethyl acetate (2×35 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-995c33c90a18485ba869e9d0b89019ae
Source dataset
uspto-grants-2007_11
Patent number
US07301028B2

Reaction notes

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