Butyl vinyl ether → HCID 59822296, compound

HRID 1670515Notes

Reaction equation

HRID 1670515 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[CH:27]([O:29]CCCC)=[CH2:28].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)C.CN(C=O)C>[C:27]([C:3]1[C:4]2[CH2:10][CH2:9][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:7][CH2:6][C:5]=2[CH:17]=[CH:18][C:2]=1[Cl:1])(=[O:29])[CH3:28]

Participants

8

Reactant 4

HCID 8108Butyl vinyl etherHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 59822296HCID 59822296, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Combine 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.6 g, 1.41 mmol), butyl vinyl ether (0.9 mL, 7.06 mmol), palladium(II) acetate (32 mg, 0.14 mmol), DPPP (58 mg, 0.14 mmol), triethylamine (90.4 mL, 2.82 mmol), anhydrous DMF (10 mL) and stir at 90° C. for 2 h. Cool the reaction mixture to room temperature, add diethyl ether (25 mL) and wash with brine (15 mL). Separate the organic layer, dry over anhydrous Na2SO4, filter and concentrate in vacuo. Dissolve the residue in methanol (20 mL), add 1N aqueous HCl (18 mL) and stir at 70° C. for 2 h. Cool the reaction mixture to room temperature and remove methanol by evaporation. Dissolve the residue in diethyl ether (20 mL), wash with brine, collect the organic layer and dry over Na2SO4. Concentrate in vacuo and purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 3:2 gradient) to obtain the desired intermediate as a colorless oil (0.4 g, 90%). MS (ES+) m/z: 320 (M+H)+.

Workup

  1. washwash with brine (15 mL)
  2. customSeparate the organic layer
  3. dry with materialdry over anhydrous Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the residue in methanol (20 mL)
  7. additionadd 1N aqueous HCl (18 mL)
  8. temperatureCool the reaction mixture to room temperature
  9. customremove methanol
  10. customby evaporation
  11. dissolutionDissolve the residue in diethyl ether (20 mL)
  12. washwash with brine
  13. customcollect the organic layer
  14. dry with materialdry over Na2SO4
  15. concentrationConcentrate in vacuo
  16. custompurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 3:2 gradient)

Sources & evidence

ORD record
ord-9bc560a27b8342baa03269fc6afddbc0
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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