Benzyl Bromide → (1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-benzyl ester 2-tert-butyl ester

HRID 1052129Notes

Reaction equation

HRID 1052129 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]([OH:16])=[O:15])[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]([O:16][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:15])[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 11020613(1R,3S,5R)-2-(tert-Butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid

Product 1

HCID 68283955(1R,3S,5R)-2-Aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-benzyl ester 2-tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (1R,3S,5R)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester (2.5 g, 11.0 mmol) and Cs2CO3 (3.94 g, 12.1 mmol) in DMF (50 mL) at 0° C. benzylbromide (2.26 g, 13.2 mmol) was added dropwise. The reaction mixture was stirred overnight at RT under a nitrogen atmosphere. DMF was evaporated. The residue was dissolved in EtOAc and washed with a sat. aq. solution of NaHCO3, the layers were separated and the aqueous phase was extracted with EtOAc (×2). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 100:0 to 0:100) to give the desired material as a colorless oil. MS (LCMS): 318.2 [M+H]+; tR (HPLC conditions b): 2.23 min.

Workup

  1. customDMF was evaporated
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with a sat. aq. solution of NaHCO3
  4. customthe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (×2)
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 100:0 to 0:100)

Sources & evidence

ORD record
ord-a2ce4d6289544fb0b1723e51910db0d4
Source dataset
uspto-grants-2016_07
Patent number
US09388199B2

Reaction notes

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