Potassium Carbonate → 2,2-Dimethylpropionic acid 2-[(S)-3-(5-fluoro-2-nitrophenylamino)piperidin-1-yl]ethyl ester

HRID 243033Notes

Reaction equation

HRID 243033 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH2:9][O:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:3]1.F[C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[N+:25]([O-:27])=[O:26].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:24][C:22]1[CH:21]=[CH:20][C:19]([N+:25]([O-:27])=[O:26])=[C:18]([NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH2:9][O:10][C:11](=[O:16])[C:12]([CH3:13])([CH3:15])[CH3:14])[CH2:3]2)[CH:23]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 679672,4-DifluoronitrobenzeneHCID 681575062,2-dimethylpropionic acid 2-((S)-3-aminopiperidin-1-yl)ethyl ester

Product 1

HCID 681569292,2-Dimethylpropionic acid 2-[(S)-3-(5-fluoro-2-nitrophenylamino)piperidin-1-yl]ethyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled solution of 2,2-dimethylpropionic acid 2-((S)-3-aminopiperidin-1-yl)ethyl ester (1.565 g, 6.85 mmol) in DMF (30 mL) was added 2,4-difluoronitrobenzene (1.517 g, 8.92 mmol) and potassium carbonate (1.9 g, 13.8 mmol). The reaction mixture was stirred at RT for 16 h, then partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic fractions washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, eluant 10-40% EtOAc in cyclohexane) affording the title compound as a yellow oil (2.307 g, 92%). LCMS (Method J): RT 2.34 min [M+H]+ 368.

Workup

  1. custompartitioned between water and EtOAc
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washthe combined organic fractions washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, eluant 10-40% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-d215bc8525b14f7d808e65df04969cea
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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