Toluene → 4-Fluoro-1-nitro-6,7,8,9-tetrahydro-5-oxa-9-azabenzocycloheptene

HRID 243227Notes

Reaction equation

HRID 243227 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([F:18])=[CH:16][CH:15]=[C:14]([N+:19]([O-:21])=[O:20])[C:13]=1F)(C)(C)C.C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[F:18][C:17]1[C:12]2[O:11][CH2:10][CH2:9][CH2:8][NH:7][C:13]=2[C:14]([N+:19]([O-:21])=[O:20])=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 68157251[3-(2,6-Difluoro-3-nitrophenoxy)propyl]carbamic acid tert-butyl ester

Product 1

HCID 681580754-Fluoro-1-nitro-6,7,8,9-tetrahydro-5-oxa-9-azabenzocyclohepteneYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cold solution of [3-(2,6-difluoro-3-nitrophenoxy)propyl]carbamic acid tert-butyl ester (296 mg, 0.8907 mmol) in DCM (15 mL) was added TFA (3 mL). The reaction mixture was stirred at RT for 2 h, then toluene was added and volatiles were removed under reduced pressure. The resulting residue was dissolved in acetonitrile (6 mL), 2M Na2CO3 (6 mL) was added and the mixture stirred at RT for 1.5 h. The reaction mixture was partitioned between EtOAc and brine, the organic phase was dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (Si—PCC, eluant 10-20% EtOAc in cyclohexane) affording the title compound as a red solid (158.4 mg, 84%). 1H NMR (CDCl3, 300 MHz): 8.08 (1H, bs), 7.87 (1H, dd, J=9.6, 5.6 Hz), 6.44 (1H, dd, J=9.8, 8.7 Hz), 4.40 (2H, t, J=6.6 Hz), 3.78-3.73 (2H, m), 2.29-2.20 (2H, m)

Workup

  1. customvolatiles were removed under reduced pressure
  2. dissolutionThe resulting residue was dissolved in acetonitrile (6 mL)
  3. addition2M Na2CO3 (6 mL) was added
  4. stirringthe mixture stirred at RT for 1.5 h
  5. customThe reaction mixture was partitioned between EtOAc and brine
  6. dry with materialthe organic phase was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (Si—PCC, eluant 10-20% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-a3b065e7ced845ca80239c2752daf865
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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