Potassium tert-butoxide → 5-(5-Bromo-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one

HRID 81608Notes

Reaction equation

HRID 81608 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)([C:16]([F:20])([F:19])[CH2:17][OH:18])[CH3:15])[CH:13]=1>CC(O)(C)C>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([F:26])=[C:12]([C:14]2([CH3:15])[C:16]([F:20])([F:19])[CH2:17][O:18][CH2:23][C:22](=[O:25])[NH:21]2)[CH:13]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 66665738N-(2-(5-bromo-2-fluorophenyl)-3,3-difluoro-4-hydroxybutan-2-yl)-2-chloroacetamide

Product 1

HCID 666660575-(5-Bromo-2-fluorophenyl)-6,6-difluoro-5-methyl-1,4-oxazepan-3-one

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a solution of t-BuOK (0.36 g, 3.2 mmol) in t-BuOH (10 mL) was added N-(2-(5-bromo-2-fluorophenyl)-3,3-difluoro-4-hydroxybutan-2-yl)-2-chloroacetamide (1.0 g, 2.6 mmol) t-BuOH (10 mL) at rt and heated to reflux temperature for 1 h 30 min. Reaction mixture was monitored by TLC analysis. Reaction mixture was concentrated under reduced pressure and adjusted pH to −2 using 2 N HCl. Ethyl acetate was added to extract the product, organic layer was washed with water, brine solution followed by drying over anhy. Na2SO4 and concentrated under reduced pressure. The crude compound (0.9 g) was carried forward for the next step without purification. LCMS: RtH8=1.616 [M+H]+=337.8, 339.9 (56%); 1.482 [M+H]+=675.1, 676.8 (34%).

Workup

  1. temperatureheated
  2. temperatureto reflux temperature for 1 h 30 min
  3. customReaction mixture
  4. customReaction mixture
  5. concentrationwas concentrated under reduced pressure and adjusted pH to −2 using 2 N HCl
  6. additionEthyl acetate was added
  7. extractionto extract the product, organic layer
  8. washwas washed with water, brine solution
  9. customby drying over anhy
  10. concentrationNa2SO4 and concentrated under reduced pressure
  11. customThe crude compound (0.9 g) was carried forward for the next step without purification

Sources & evidence

ORD record
ord-4f03ebfc286e44abbfae37379f65d52a
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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