Dimethylformamide → Tert-butyl 4-(2-fluoro-3-formylbenzoyl)piperazine-1-carboxylate

HRID 1172452Notes

Reaction equation

HRID 1172452 reaction equation
Br[C:2]1[C:3]([F:23])=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:6].C([Mg]Cl)C(C)C.CN(C)[CH:32]=[O:33].[Cl-].[NH4+]>O1CCCC1>[F:23][C:3]1[C:2]([CH:32]=[O:33])=[CH:22][CH:21]=[CH:20][C:4]=1[C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 57562603Tert-butyl 4-(3-bromo-2-fluorobenzoyl)piperazine-1-carboxylateHCID 178418368HCID 178418368, compound

Product 1

HCID 57562639Tert-butyl 4-(2-fluoro-3-formylbenzoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

194 mg of tert-butyl 4-(3-bromo-2-fluorobenzoyl)piperazine-1-carboxylate was dissolved in 5.0 ml of tetrahydrofuran, and 1.25 ml of a solution of isobutyl magnesium chloride in tetrahydrofuran (2.0 M) was added thereto at −78° C. After stirring at the same temperature for 2 hours, 0.39 ml (5.0 mmol) of N,N-dimethylformamide was added thereto. The resulting mixture was stirred at the same temperature for 30 minutes and further stirred at 0° C. for 30 minutes. To the reaction mixture was added saturated ammonium chloride, and the mixture was extracted with chloroform. The organic layer was washed with brine and then concentrated. The residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 1/1) to give the title compound.

Workup

  1. customat −78° C
  2. stirringThe resulting mixture was stirred at the same temperature for 30 minutes
  3. stirringfurther stirred at 0° C. for 30 minutes
  4. extractionthe mixture was extracted with chloroform
  5. washThe organic layer was washed with brine
  6. concentrationconcentrated
  7. customThe residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 1/1)

Sources & evidence

ORD record
ord-8101c7d7376a4209950002c7019f1b76
Source dataset
uspto-grants-2010_11
Patent number
US07834018B2

Reaction notes

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