Potassium Carbonate → HCID 58919227, compound

HRID 539710Notes

Reaction equation

HRID 539710 reaction equation
Br[CH2:2][C:3]1[C:4]([F:14])=[C:5]([C:10]([F:13])=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7].[N:15]1([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[F:14][C:4]1[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:10]([F:13])[CH:11]=[CH:12][C:3]=1[CH2:2][N:18]1[CH2:17][CH2:16][N:15]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 58919229942224-45-5

Product 1

HCID 58919227HCID 58919227, compoundYield 41.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a room temperature solution of methyl 3-(bromomethyl)-2,6-difluorobenzoate (14.24 g, nominally 51.2 mmol, 1.0 equiv) and tert-butyl piperazine-1-carboxylate (9.1 g, 50.24 mmol, 1.0 equiv) in DMF (50 mL) was added K2CO3 (27.8 g, 201 mmol, 4.0 equiv) as a solid. The resulting mixture was allowed to stir overnight. The reaction mixture was diluted with EtOAc and washed repeatedly with H2O. The combined aqueous layers were washed once with EtOAc, and the combined organic layers were washed once with brine, dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel chromatography (10%-60% EtOAc/hexanes) provided tert-butyl 4-(2,4-difluoro-3-(methoxycarbonyl)benzyl)piperazine-1-carboxylate (7.70 g, 41.4% over two steps). LCMS m/z (APCI)=371.2 (M+H).

Workup

  1. washwashed repeatedly with H2O
  2. washThe combined aqueous layers were washed once with EtOAc
  3. washthe combined organic layers were washed once with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8b81470da70c416aa96c87e5647a6cfd
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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