2-Benzyl 1-tert-butyl (2S)-5-oxopyrrolidine-1,2-dicarboxylate → 2-Tert-butoxycarbonylamino-5-(3,4-dimethoxy-phenyl)-5-oxo-pentanoic acid benzyl ester

HRID 967038Notes

Reaction equation

HRID 967038 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@H:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([Mg]Br)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33]>C1COCC1>[CH2:17]([O:16][C:14](=[O:15])[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10][CH2:11][C:12]([C:29]1[CH:28]=[CH:27][C:26]([O:25][CH3:24])=[C:31]([O:32][CH3:33])[CH:30]=1)=[O:13])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 80274822-Benzyl 1-tert-butyl (2S)-5-oxopyrrolidine-1,2-dicarboxylateHCID 178491916HCID 178491916, compound

Product 1

HCID 691554772-Tert-butoxycarbonylamino-5-(3,4-dimethoxy-phenyl)-5-oxo-pentanoic acid benzyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (2S)5-oxo-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (8.20 g, 0.026 mol, 1.0 equivalent) in anhydrous THF was cooled to 0° C. in an ice bath under N2. A chilled 0.5M solution of 3,4-dimethoxyphenylmagnesium bromide in THF (52.1 mL, 0.026 mol, 1.0 equivalent) was slowly added. The reaction mixture was allowed to stir for two hours. The reaction was quenched upon addition of saturated NH4Cl solution (10 ml). The mixture was partitioned between ethyl acetate and brine. The organic extract was washed with brine (3×100 ml). The ethyl acetate layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting crude blue oil was filtered through a layer of silica. The filtrate was concentrated in vacuo to afford 2-tert-butoxycarbonylamino-5-(3,4-dimethoxy-phenyl)-5-oxo-pentanoic acid benzyl ester (10.46 g, 0.023 mol, 88% yield). Analysis H1 NMR (400 MHz, CDCl3): 7.5-7.3 (6H, m), 7.0-6.7 (2H, m), 5.2 (2H, m), 4.0-3.8 (6H, m), 3.0 (1H, m), 2.6-1.9 (4H, m), 1.4 (9H, s). MS (LC-MS): Calculated for C25H31NO7 457.21, found 458.19 (M+H)+.

Workup

  1. customThe reaction was quenched upon addition of saturated NH4Cl solution (10 ml)
  2. customThe mixture was partitioned between ethyl acetate and brine
  3. extractionThe organic extract
  4. washwas washed with brine (3×100 ml)
  5. dry with materialThe ethyl acetate layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. filtrationThe resulting crude blue oil was filtered through a layer of silica
  8. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-1c430d96b1ce41dd9c3a5dd070e9d860
Source dataset
uspto-grants-2005_10
Patent number
US06953801B2

Reaction notes

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