Potassium Carbonate → (S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407999Notes

Reaction equation

HRID 407999 reaction equation
CS([O:5][C@@H:6]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[C:7]1=[O:24])(=O)=O.C(=O)([O-])[O-].[K+].[K+].[F:31][C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][C:41]=1O)[C:35]([O:37][CH3:38])=[O:36]>CN(C=O)C.O>[F:31][C:32]1[CH:33]=[C:34]([C:35]([O:37][CH3:38])=[O:36])[CH:39]=[CH:40][C:41]=1[O:5][C@H:6]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[C:7]1=[O:24]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 7019368Methyl 3-fluoro-4-hydroxybenzoateHCID 86688072(R)-tert-butyl 4-(3-(methylsulfonyloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

Product 1

HCID 86688102(S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateYield 83.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

(Step A: To a solution of (R)-tert-butyl 4-(3-(methylsulfonyloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (Preparation D; 2 g, 5.5 mmol) in DMF (20 mL) was added potassium carbonate (0.99 g, 7.2 mmol) and methyl 3-fluoro-4-hydroxybenzoate (1.1 g, 6.6 mmol) and the reaction was heated to 60° C. overnight. The reaction was diluted with water (100 mL) and extracted with EtOAc (100 mL). The organic layer was washed with 1 N NaOH (20 mL), and brine (20 mL), dried over MgSO4, filtered and concentrated under vacuum to give (S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (2 g, 83%).

Workup

  1. extractionextracted with EtOAc (100 mL)
  2. washThe organic layer was washed with 1 N NaOH (20 mL), and brine (20 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-665b604533a04a9f985e6a9fdb4eead0
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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