Sodium hydride → ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate

HRID 595216

Reaction equation

HRID 595216 reaction equation
[CH3:1][CH:2]1[CH:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:5][C:4](=[O:12])[NH:3]1.[H-].[Na+].[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][CH:18]=1.[I-].C([NH3+])(C)(C)C>CN(C=O)C>[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][N:3]2[C:4](=[O:12])[CH2:5][CH:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:2]2[CH3:1])=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 22344722t-Butylammonium IodideHCID 118208888Ethyl rac-(2R,3S)-2-methyl-5-oxopyrrolidine-3-carboxylate

Product 1

HCID 118208506ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Ethyl rac-(2R,3S)-2-methyl-5-oxopyrrolidine-3-carboxylate (30 g, 0.18 mol) in DMF (100 mL) was carefully added to a suspension of sodium hydride (7.6 g, 0.19 mol, 60% in mineral oil) in DMF (400 mL) at 0° C. The resulting mixture was stirred for 1 hour before 4-methoxybenzyl chloride (32.8 g, 28.5 mL, 0.21 mol) was added dropwise, followed by tert-butylammonium iodide (13 g, 35 mmol). The reaction mixture was stirred at room temperature for 10 hours and then quenched by adding saturated aqueous ammonium chloride solution (30 mL). The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (500 mL×3). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to afford ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate. MS ESI calc'd. for C16H22NO4 [M+H]+ 292. found 292. 1H NMR (CDCl3, 400 MHz) δ: 7.13 (d, J=8.4 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.91 (d, J=14.4 Hz, 1H), 4.08-4.15 (m, 2H), 3.89 (d, J=14.4 Hz, 1H), 3.76 (s, 3H), 3.62-3.63 (m, 1H), 2.71 (s, 3H), 1.18-1.26 (m, 6H).

Workup

  1. additionwas added dropwise
  2. customquenched
  3. additionby adding saturated aqueous ammonium chloride solution (30 mL)
  4. additionThe reaction mixture was diluted with water (100 mL)
  5. extractionextracted with ethyl acetate (500 mL×3)
  6. washThe combined organic layers were washed with brine (100 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford the crude product, which
  11. customwas purified by chromatography on silica gel (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-c31036f516b24df386a9fa0188c606b7
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Linked notes

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