Cesium carbonate → rac-(4R,5R)-4-[(4-iodo-1H-pyrazol-1-yl)methyl]-1-(4-methoxybenzyl)-5-methylpyrrolidin-2-one

HRID 595219Notes

Reaction equation

HRID 595219 reaction equation
[I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:18][C@H:19]1[CH2:23][C:22](=[O:24])[N:21]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C@@H:20]1[CH3:34])(=O)=O>CN(C=O)C.O>[I:1][C:2]1[CH:3]=[N:4][N:5]([CH2:18][CH:19]2[CH:20]([CH3:34])[N:21]([CH2:25][C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)[C:22](=[O:24])[CH2:23]2)[CH:6]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 770224-IodopyrazoleHCID 118208685[(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidin-3-yl]methyl rac-methanesulfonate

Product 1

HCID 118208932rac-(4R,5R)-4-[(4-iodo-1H-pyrazol-1-yl)methyl]-1-(4-methoxybenzyl)-5-methylpyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

4-Iodo-1H-pyrazole (0.93 g, 4.77 mmol) and cesium carbonate (2.59 g, 7.95 mmol) were added to a solution of [(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidin-3-yl]methyl rac-methanesulfonate (1.3 g, 3.98 mmol) in DMF (26 mL). The mixture was stirred at 90° C. under a nitrogen atmosphere for 3 hours. After cooling to room temperature, the mixture was diluted with water (50 mL) and extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to afford rac-(4R,5R)-4-[(4-iodo-1H-pyrazol-1-yl)methyl]-1-(4-methoxybenzyl)-5-methylpyrrolidin-2-one. MS ESI calc'd. for C17H21IN3O2 [M+H]+ 426. found 426. 1H NMR (400 MHz, CDCl3): δ 7.47 (s, 1H), 7.17 (d, J=8.5 Hz, 2H), 6.95 (s, 1H), 6.90 (d, J=8.5 Hz, 2H), 4.99-4.94 (m, 1H), 4.02-3.99 (m, 1H), 3.90-3.85 (m, 1H), 3.85 (s, 3H), 3.82-3.79 (m, 1H), 3.15-3.06 (m, 1H), 2.69-2.63 (m, 1H), 2.58-2.48 (m, 1H), 2.18-2.09 (m, 1H), 1.06 (d, J=6.5 Hz, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate (100 mL×3)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-2dc9eeff78a7458ea8092df1e3870e05
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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