Water → (2S,4R)-2-benzooxazol-2-yl-4-tert-butoxy-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1477536Notes

Reaction equation

HRID 1477536 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][C@H:12]1[C:21](=[O:30])[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1Br)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>COCCOC.[Cu]I>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:13][C@H:12]1[C:21]1[O:30][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 10796Cesium carbonateHCID 89768141(2S,4R)-2-(2-bromo-phenylcarbamoyl)-4-tert-butoxy-pyrrolidine-1-carboxylic acid benzyl ester

Product 1

HCID 89768034(2S,4R)-2-benzooxazol-2-yl-4-tert-butoxy-pyrrolidine-1-carboxylic acid benzyl esterYield 57.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred solution of (2S,4R)-2-(2-bromo-phenylcarbamoyl)-4-tert-butoxy-pyrrolidine-1-carboxylic acid benzyl ester (900 mg, 1.89 mmol) in DME (20 mL) at 25° C. in a sealed tube were added CuI (36 mg, 0.19 mmol), 1,10-phenanthraline (68 mg, 0.38 mmol), and Cs2CO3 (1.847 g, 5.68 mmol). The reaction mixture was refluxed for 14 h. After completion of reaction, water was added, and the mixture was then extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude was then purified by column chromatography to give (2S,4R)-2-benzooxazol-2-yl-4-tert-butoxy-pyrrolidine-1-carboxylic acid benzyl ester (430 mg, 57.5% yield) as a yellowish liquid. MS calcd. for C23H27N2O4 [(M+H)+] 395, obsd. 395.

Workup

  1. temperatureThe reaction mixture was refluxed for 14 h
  2. additionwas added
  3. extractionthe mixture was then extracted with dichloromethane
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was then purified by column chromatography

Sources & evidence

ORD record
ord-b8f63538130f44068a8e7713d95596e8
Source dataset
uspto-grants-2016_08
Patent number
US09403805B2

Reaction notes

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