Potassium Carbonate → 4-chloro-N-[(1R)-1-cyclopropylethyl]-2,5-difluorobenzamide

HRID 2363313Notes

Reaction equation

HRID 2363313 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[C:16]([F:17])=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([F:18])[CH:9]=1.C(=O)([O-])[O-].[K+].[K+].[CH:25]1([C@H:28]([NH2:30])[CH3:29])[CH2:27][CH2:26]1>O.C(Cl)Cl.CN(C=O)C>[Cl:7][C:8]1[C:16]([F:17])=[CH:15][C:11]([C:12]([NH:30][C@@H:28]([CH:25]2[CH2:27][CH2:26]2)[CH3:29])=[O:14])=[C:10]([F:18])[CH:9]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 27332744-Chloro-2,5-difluorobenzoic acidHCID 7016286(R)-1-Cyclopropylethylamine

Product 1

HCID 712080524-chloro-N-[(1R)-1-cyclopropylethyl]-2,5-difluorobenzamideYield 96.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (250.0 μL, 2.954 mmol) was added to a solution of 4-chloro-2,5-difluorobenzoic acid (0.0578 g, 0.300 mmol) in dichloromethylene (3 mL), followed by 15 μL of DMF. The mixture was stirred at room temperature for 1 hour. The volatiles were removed under reduced pressure. The residue was diluted with dichloromethylene (5 mL). To the solution was added potassium carbonate (82.9 mg, 0.600 mmol) in water (1 mL), and (1R)-1-cyclopropylethanamine (41.6 μL, 0.450 mmol). The mixture was stirred at room temperature for 30 minutes, and diluted with DCM, washed with water and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to afford the desired product (0.075 g, 96%) which was directly used in the next step reaction without further purification. LCMS (M+H)+: m/z=260.0.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. additionThe residue was diluted with dichloromethylene (5 mL)
  3. stirringThe mixture was stirred at room temperature for 30 minutes
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-227c3b09f4f448b49345ec1276df529b
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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