Water → Ethyl 2-(1-(4-(Benzyloxy)-2-nitrophenyl)-2-oxopyrrolidin-3-yl)acetate

HRID 1964091Notes

Reaction equation

HRID 1964091 reaction equation
[O:1]=[C:2]1[CH:6]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:5][CH2:4][NH:3]1.[H-].[Na+].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26](F)=[C:25]([N+:30]([O-:32])=[O:31])[CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>CN(C=O)C>[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([N:3]2[CH2:4][CH2:5][CH:6]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:2]2=[O:1])=[C:25]([N+:30]([O-:32])=[O:31])[CH:24]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 442030064-(Benzyloxy)-1-fluoro-2-nitrobenzeneHCID 66847687Ethyl 2-(2-oxopyrrolidin-3-yl)acetate

Product 1

HCID 67249168Ethyl 2-(1-(4-(Benzyloxy)-2-nitrophenyl)-2-oxopyrrolidin-3-yl)acetateYield 26.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 2-(2-oxopyrrolidin-3-yl)acetate (1.77 g, 10.34 mmol) was dissolved in DMF (20 mL) and cooled to 0° C. Sodium hydride (60% in mineral oil, 0.414 g, 10.34 mmol) was added. After stirring for several min, the reaction was allowed to warm to room temperature and stirred for 10 min. 4-(Benzyloxy)-1-fluoro-2-nitrobenzene (2.56 g, 10.34 mmol) was added and the mixture was stirred at room temperature for 21 h. The reaction was poured into water and acidified to pH 5 with 1.0 M HCL. The aqueous mixture was extracted three times with EtOAc and the combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to provide the title compound (1.09 g). LCMS m/z=399.4 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.27 (t, J=7.2 Hz, 3H), 1.97-2.01 (m, 1H), 2.46-2.59 (m, 2H), 2.95 (dd, J=12.9, 3.8 Hz, 1H), 2.96-3.06 (m, 1H), 3.69-3.76 (m, 1H), 3.79-3.88 (m, 1H), 4.17 (q, J=7.1 Hz, 2H), 5.13 (s, 2H), 6.90 (d, J=2.5 Hz, 1H), 6.94 (dd, J=9.0, 2.7 Hz, 1H), 7.37-7.42 (m, 5H), 8.04 (d, J=9.1 Hz, 1H).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 10 min
  3. stirringthe mixture was stirred at room temperature for 21 h
  4. extractionThe aqueous mixture was extracted three times with EtOAc
  5. dry with materialthe combined extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-2106ea46a933461caf1ffd6ee3a3fc76
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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