Chlorotrimethylsilane → HCID 86713317, compound

HRID 927976Notes

Reaction equation

HRID 927976 reaction equation
BrCCBr.Cl[Si](C)(C)C.I[CH:11]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]1.[F:22][C:23]1[CH:24]=[C:25](I)[CH:26]=[CH:27][CH:28]=1>CN(C=O)C.O.C(OCC)(=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>[F:22][C:23]1[CH:28]=[C:27]([CH:11]2[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]2)[CH:26]=[CH:25][CH:24]=1

Participants

11

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 707251-Fluoro-3-iodobenzeneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylate

Product 1

HCID 86713317HCID 86713317, compoundYield 56.8%

Reagents, catalysts & solvents 6

HCID 23994ZincCatalystHCID 521585Tris(furan-2-yl)phosphaneCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1,2-dibromoethane (0.30 g) in anhydrous DMF (25 ml) was stirred with zinc dust (1.39 g) at 70° C. for 10 minutes then cooled to room temperature and chlorotrimethylsilane was (0.155 g) added. The resultant mixture was stirred at room temperature for 45 minutes. tert-Butyl 3-iodoazetidine-1-carboxylate (5 g) added and stirring was continued at 40° C. for 45 minutes then a solution of 3-fluoroiodobenzene (4.08 g), tris(dibenzylideneacetone)dipalladium(0) (0.325 g) and tris(2-furyl)phosphine (0.165 g) in DMF (15 mL) was added and the mixture was stirred at 70° C. for 3 hours. After cooling, the mixture was diluted with water and ethyl acetate and filtered through celite. The organic layer was washed twice with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-10%. The crude product was further purified by chromatography on silica, eluting with a mixture of DCM and cyclohexane with a gradient of 0-100% to give tert-butyl 3-(3-fluorophenyl)azetidine-1-carboxylate (2.52 g) as a colourless oil.

Workup

  1. additionadded
  2. stirringthe mixture was stirred at 70° C. for 3 hours
  3. temperatureAfter cooling
  4. filtrationfiltered through celite
  5. washThe organic layer was washed twice with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-10%
  11. customThe crude product was further purified by chromatography on silica
  12. washeluting with a mixture of DCM and cyclohexane with a gradient of 0-100%

Sources & evidence

ORD record
ord-5e714016a4824c799e242e95fb72938c
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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