Benzyl Bromide → 2-benzyl 1-tert-butyl (2S,3R)-3-hydroxypyrrolidine-1,2-dicarboxylate

HRID 1527324Notes

Reaction equation

HRID 1527324 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([OH:13])[C@H:9]1[C:14]([OH:16])=[O:15])=[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>CO.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([OH:13])[C@H:9]1[C:14]([O:16][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 11096439(2S,3R)-3-Hydroxypyrrolidine-2-carboxylic acid, N-BOC protected

Product 1

HCID 109252822-benzyl 1-tert-butyl (2S,3R)-3-hydroxypyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2S,3R)-3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester [186132-96-7] (500 mg, 2.162 mmol; Chem-Impex International, Inc.) in MeOH (9.0 mL), cooled to 0° C., was added with stirring a solution of Cs2CO3 (704 mg, 2.162 mmol) in water (6.0 mL). The mixture was concentrated by rotary evaporation and the residue was suspended in DMF (17.0 mL). The suspension was cooled to 0° C., followed by addition of benzylbromide (0.514 mL, 4.32 mmol) and stirring overnight at RT. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was dissolved in EtOAc. The organics were washed with aqueous NaHCO3 (2×) and water (2×), dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 2:3) to give the title compound as an oil. MS (LC/MS): 322 [M+H]+, 665 [2M+Na]+; tR (HPLC conditions b): 4.12 min.

Workup

  1. additionwas added
  2. concentrationThe mixture was concentrated by rotary evaporation
  3. filtrationThe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in EtOAc
  6. washThe organics were washed with aqueous NaHCO3 (2×) and water (2×)
  7. customdried (Phase separator)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 2:3)

Sources & evidence

ORD record
ord-1a68fa61214e4aefbe0867096d7a8da4
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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