Triphosgene → Tert-butyl (1-(4'-fluoro-4-nitrobiphenyl-3-ylcarbamoyl)azetidin-3-yl)methylcarbamate

HRID 62705Notes

Reaction equation

HRID 62705 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([NH2:17])[CH:9]=2)=[CH:4][CH:3]=1.Cl[C:19](Cl)([O:21]C(=O)OC(Cl)(Cl)Cl)Cl.[NH:30]1[CH2:33][CH:32]([CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:31]1>C(Cl)Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[C:38]([O:37][C:36](=[O:42])[NH:35][CH2:34][CH:32]1[CH2:33][N:30]([C:19](=[O:21])[NH:17][C:10]2[CH:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH:13]=[CH:12][C:11]=2[N+:14]([O-:16])=[O:15])[CH2:31]1)([CH3:39])([CH3:41])[CH3:40]

Participants

6

Reactant 3

HCID 94429TriphosgeneHCID 15346872tert-butyl N-(azetidin-3-ylmethyl)carbamateHCID 71818257[1,1'-Biphenyl]-3-amine, 4'-fluoro-4-nitro-

Product 1

HCID 71007318Tert-butyl (1-(4'-fluoro-4-nitrobiphenyl-3-ylcarbamoyl)azetidin-3-yl)methylcarbamateYield 69.7%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4′-fluoro-4-nitro-[1,1′-biphenyl]-3-amine (1.5 g, 6.46 mmol) in DCM (50 mL) were added triphosgene (1.917 g, 6.46 mmol) and TEA (8.5 g, 84 mmol) at 0° C. The reaction mixture was stirred at room temperature for two hours. tert-butyl azetidin-3-ylmethylcarbamate (1.203 g, 6.46 mmol) was then added at 0° C. and the reaction mixture was stirred at room temperature for four hours. The reaction crude was diluted with saturated citric acid solution and extracted with DCM. The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated to yield crude residue which was purified by column chromatography eluting with 30% EtOAc in Hexane to afford tert-butyl((1-((4′-fluoro-4-nitro-[1,1′-biphenyl]-3-yl)carbamoyl)azetidin-3-yl)methyl)carbamate (2 g, 69.7% yield).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for four hours
  2. customThe reaction crude
  3. extractionextracted with DCM
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield crude residue which
  9. customwas purified by column chromatography
  10. washeluting with 30% EtOAc in Hexane

Sources & evidence

ORD record
ord-803b27dd5bef424dae76ae18aee9c735
Source dataset
uspto-grants-2016_09
Patent number
US09447030B2

Reaction notes

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