Benzyl Bromide → (S)-2,5-Dihydro-pyrrole-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

HRID 1527403Notes

Reaction equation

HRID 1527403 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]=[CH:10][C@H:9]1[C:13]([OH:15])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]=[CH:10][C@H:9]1[C:13]([O:15][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:14])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 688391(S)-1-(tert-Butoxycarbonyl)-2,5-dihydro-1H-pyrrole-2-carboxylic acid

Product 1

HCID 58815105(S)-2,5-Dihydro-pyrrole-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-1-(tert-butoxycarbonyl)-2,5-dihydro-1H-pyrrole-2-carboxylic acid (10 g, 46.9 mmol) in DMF (249 mL) cooled at 0° C. were added cesium carbonate (16.8 g, 51.6 mmol) then benzyl bromide (6.69 mL, 56.3 mmol) and the mixture was allowed to warm up to RT overnight. The reaction mixture was quenched with water (500 mL) and extracted with ethyl acetate (3×200 mL). The organic layers were combined and washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 4:1) to give the desired material. TLC, Rf (c-hexane/EtOAc 4:1)=0.25; MS (UPLC): 326 [M+Na]+, 204 [MH−Boc]+; tR (HPLC conditions f): 2.35 min.

Workup

  1. customThe reaction mixture was quenched with water (500 mL)
  2. extractionextracted with ethyl acetate (3×200 mL)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-e02d858aef1d42709ecfae1629afdb53
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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