Dimethylformamide → HCID 86666498, compound

HRID 1426303Notes

Reaction equation

HRID 1426303 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[C:20]([F:22])[CH:21]=1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.C([Li])CCC.CCCCCC.CN(C)[CH:36]=[O:37]>C1COCC1>[F:22][C:20]1[CH:19]=[C:4]([CH:3]=[C:2]([CH:36]=[O:37])[CH:21]=1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8058HexaneHCID 69673392HCID 69673392, compoundHCID 178418339Butyllithium

Product 1

HCID 86666498HCID 86666498, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-(3-bromo-5-fluorophenoxy)piperidine-1-carboxylate (0.666 g, 1.78 mmol) in THF (9.0 mL) at −78° C. was added 2.5M n-butyllithium in hexane (0.78 mL, 2.0 mmol). The solution was stirred at same temperature for 30 minutes, then N,N-dimethylformamide (1.4 mL, 18 mmol) was added to reaction flask. The reaction solution was allowed to warm to room temperature and stirred overnight. The reaction was quenched with water, and aqueous layer was extracted with ethyl acetate twice. The combined organic solutions were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was diluted with methanol and purified with prep-LCMS (C18 column eluting with a gradient of ACN/H2O containing 0.15% NH4OH) to give the desired product as an oil (75 mg, 13%). LCMS (M+H-100)+: 224.1.

Workup

  1. stirringstirred overnight
  2. customThe reaction was quenched with water, and aqueous layer
  3. extractionwas extracted with ethyl acetate twice
  4. washThe combined organic solutions were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionThe residue was diluted with methanol
  9. custompurified with prep-LCMS (C18 column
  10. washeluting with a gradient of ACN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-5bda1736ab2a485195e6ad2db647bd06
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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