(2e)-3-{2,6-Difluoro-4-[(isopropoxycarbonyl)amino]phenyl}prop-2-enyl diazoacetate → (Racemic)isopropyl 3,5-difluoro-4-[(1s,5r,6r)-2-oxo-3-oxabicyclo[3.1.0]hex-6-yl]phenylcarbamate

HRID 1179483Notes

Reaction equation

HRID 1179483 reaction equation
[N+](=[CH:3][C:4]([O:6][CH2:7]/[CH:8]=[CH:9]/[C:10]1[C:15]([F:16])=[CH:14][C:13]([NH:17][C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19])=[CH:12][C:11]=1[F:24])=[O:5])=[N-]>C1(C)C=CC=CC=1.ClCCl.C1(C)C=CC=CC=1.[Cu+2]>[F:24][C:11]1[CH:12]=[C:13]([NH:17][C:18](=[O:19])[O:20][CH:21]([CH3:23])[CH3:22])[CH:14]=[C:15]([F:16])[C:10]=1[C@H:9]1[C@H:3]2[C@@H:8]1[CH2:7][O:6][C:4]2=[O:5]

Participants

5

Reactant 1

HCID 131726632(2e)-3-{2,6-Difluoro-4-[(isopropoxycarbonyl)amino]phenyl}prop-2-enyl diazoacetate

Product 1

HCID 58978078(Racemic)isopropyl 3,5-difluoro-4-[(1s,5r,6r)-2-oxo-3-oxabicyclo[3.1.0]hex-6-yl]phenylcarbamate

Reagents, catalysts & solvents 3

HCID 27099Cupric cationCatalystHCID 1140TolueneSolventHCID 21877217Toluene methylene chlorideSolvent

Procedure

A solution of (2E)-3-{2,6-difluoro-4-[(isopropoxycarbonyl)amino]phenyl}prop-2-enyl diazoacetate (2.4 g, 7.07 mmol) in 170 mL of toluene/dichloromethane (1:2) was added dropwise over 14 h to a refluxing solution of bis-(N-t-butylsalicylaldiminato) copper(II) (0.147 g, 0.35 mmol) in 120 mL of toluene. After the addition was complete, the reaction mixture was heated another hour at reflux, then cooled, filtered and concentrated. The crude oil was purified by column chromatography (15-40% EtOAc-hexanes) to provide the title compound (a racemic mixture) as a yellow solid.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was heated another hour
  3. temperatureat reflux
  4. temperaturecooled
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude oil was purified by column chromatography (15-40% EtOAc-hexanes)

Sources & evidence

ORD record
ord-e404ca7b1e784837a5239aae46edba60
Source dataset
uspto-grants-2007_10
Patent number
US07279494B2

Reaction notes

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