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 1793450Notes

Reaction equation

HRID 1793450 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-89129204560a4d65af30a3ddcfdac19d
Source dataset
uspto-grants-2006_07
Patent number
US07081458B2

Reaction notes

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