Potassium tert-butoxide → 5-(5-Bromo-2-fluoro-phenyl)-5-difluoromethyl-[1,4]oxazepan-3-one

HRID 81594Notes

Reaction equation

HRID 81594 reaction equation
CC([O-])(C)C.[K+].[Br:7][C:8]1[CH:9]=[CH:10][C:11]([F:26])=[C:12]([C:14]([NH:21][C:22](=[O:25])[CH2:23]Cl)([CH:18]([F:20])[F:19])[CH2:15][CH2:16][OH:17])[CH:13]=1>CC(O)(C)C.C1COCC1>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([F:26])=[C:12]([C:14]2([CH:18]([F:20])[F:19])[CH2:15][CH2:16][O:17][CH2:23][C:22](=[O:25])[NH:21]2)[CH:13]=1

Participants

5

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 66665589N-[1-(5-bromo-2-fluoro-phenyl)-1-difluoromethyl-3-hydroxy-propyl]-2-chloro-acetamide

Product 1

HCID 666655995-(5-Bromo-2-fluoro-phenyl)-5-difluoromethyl-[1,4]oxazepan-3-one

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a refluxing solution of potassium tert-butylate (1.63 g, 14.52 mmol) in 555 ml t-BuOH was added dropwise a solution of) N-[1-(5-bromo-2-fluoro-phenyl)-1-difluoromethyl-3-hydroxy-propyl]-2-chloro-acetamide (2.72 g, 7.26 mmol) in 45 ml THF over a period of 40 minutes. The reaction mixture was cooled down and quenched with 1N HCl. EtOAc was added and the organic layer was washed with brine, dried with Na2SO4 and evaporated. The crude product was crystallized from DCM/TBME to provide the title compound as white crystals.

Workup

  1. temperatureThe reaction mixture was cooled down
  2. customquenched with 1N HCl
  3. additionEtOAc was added
  4. washthe organic layer was washed with brine
  5. dry with materialdried with Na2SO4
  6. customevaporated
  7. customThe crude product was crystallized from DCM/TBME

Sources & evidence

ORD record
ord-f7b3c930574649ce94175d4633c968ec
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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