Acetic Acid → 3-Fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)nitrobenzene

HRID 1418657Notes

Reaction equation

HRID 1418657 reaction equation
C1(C(C2C=CC=CC=2)[N:8]2[CH2:11][C:10]([O:13][CH3:14])([CH3:12])[CH2:9]2)C=CC=CC=1.C(O)(=O)C.P([O-])([O-])(O)=O.[K+].[K+].[F:32][C:33]1[CH:34]=[C:35]([N+:40]([O-:42])=[O:41])[CH:36]=[CH:37][C:38]=1F>O1CCCC1.C(O)C.CS(C)=O.O.[OH-].[OH-].[Pd+2].CCCCCC.C(OCC)(=O)C>[F:32][C:33]1[CH:34]=[C:35]([N+:40]([O-:42])=[O:41])[CH:36]=[CH:37][C:38]=1[N:8]1[CH2:11][C:10]([O:13][CH3:14])([CH3:12])[CH2:9]1

Participants

10

Reactant 4

HCID 176Acetic AcidHCID 24450Potassium Phosphate, DibasicHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 152086291-Benzhydryl-3-methoxy-3-methylazetidine

Product 1

HCID 544553723-Fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)nitrobenzeneYield 93.7%

Reagents, catalysts & solvents 5

HCID 9942167Palladium hydroxideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 21226206Ethyl acetate hexaneSolventHCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

A solution of 1-(diphenylmethyl)-3-methoxy-3-methylazetidine (2.20 g, 8.2 mmol) in 25% tetrahydrofuran/ethanol was treated with glacial acetic acid (1.60 g, 1.50 mL, 24.7 mmol) and then palladium hydroxide on carbon (0.220 g) under a nitrogen stream. The reaction mixture was shaken on a Parr apparatus under 35 psi of H2. At this time TLC analysis (9:1 hexane/ethyl acetate) revealed the reaction to be complete. The mixture was filtered through Celite® (ethyl acetate wash) and the filtrate concentrated in vacuo to give an oil. This material was dissolved in dimethyl sulfoxide (15 mL) and the solution treated with dipotassium hydrogen phosphate (8.60 g, 49.2 mmol) and 3,4-difluoronitrobenzene (1.30 g, 0.886 mL, 8.0 mmol) at ambient temperature. The yellow reaction mixture was stirred at ambient temperature under a nitrogen atmosphere for 18 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and dried in vacuo to give a yellow solid. Chromatography over silica gel, eluting with 8:1 hexane/ethyl acetate, afforded, after concentration of appropriate fractions, 1.80 g (90%) of the title compound as a yellow solid with mp 110°-111° C. and MS(EI) 240 (M+).

Workup

  1. customthe reaction
  2. filtrationThe mixture was filtered through Celite® (ethyl acetate wash)
  3. concentrationthe filtrate concentrated in vacuo
  4. customto give an oil
  5. stirringThe yellow reaction mixture was stirred at ambient temperature under a nitrogen atmosphere for 18 hours
  6. extractionextracted with dichloromethane
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customdried in vacuo
  11. customto give a yellow solid
  12. washChromatography over silica gel, eluting with 8:1 hexane/ethyl acetate
  13. customafforded

Sources & evidence

ORD record
ord-6309c6f44abb4015ad00b8459936ad13
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

Loading…