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

HRID 407953Notes

Reaction equation

HRID 407953 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.[F:25][C:26]1[CH:27]=[C:28]([CH:33]=[CH:34][C:35]=1O)[C:29]([O:31][CH3:32])=[O:30].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[F:25][C:26]1[CH:27]=[C:28]([C:29]([O:31][CH3:32])=[O:30])[CH:33]=[CH:34][C:35]=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

5

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 100%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

(R)-tert-butyl 4-(3-(methylsulfonyloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (Preparation D; 1.0 g, 2.8 mmol) was dissolved in dry DMSO (15 mL) and methyl 3-fluoro-4-hydroxybenzoate (0.56 g, 3.3 mmol) and K2CO3 (0.46 g, 3.3 mmol) were added and the reaction heated to 70° C. under nitrogen. The reaction became purple and then black. The reaction was cooled to ambient temperature after 3 hours, stirred at ambient temperature overnight, partitioned between water and EtOAc, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (60% EtOAc in hexanes) to afford (S)-tert-butyl 4-(3-(2-fluoro-4-(methoxycarbonyl)phenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.2 g, 2.7 mmol, 100% yield) as a white solid.

Workup

  1. temperatureThe reaction was cooled to ambient temperature after 3 hours
  2. custompartitioned between water and EtOAc
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified over silica gel (60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-58a5303b8abe4963b5cc31f00575271f
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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