Water → HCID 59822322, compound

HRID 1670516Notes

Reaction equation

HRID 1670516 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.C(Cl)Cl.O.[CH3:31][N:32](C=O)C>[C-]#N.[Zn+2].[C-]#N.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[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]=1[C:31]#[N:32]

Participants

8

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 6344DichloromethaneHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 59822322HCID 59822322, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

Combine 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (5.015 g, 11.8 mmol), zinc cyanide (2.09 g, 17.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.59 g, 0.59 mmol) and DPPF (0.659 g, 1.18 mmol) in anhydrous DMF (40 mL), and stir at 95° C. for 3 h. Cool the reaction mixture to room temperature, add DCM and water. Extract the aqueous phase with DCM. Dry the combined organic extracts over anhydrous Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (20:1, 10:1 and 5:1) to obtain the desired intermediate (3.2 g, 90%). MS (ES+) m/z: 303 (M+H)+.

Workup

  1. extractionExtract the aqueous phase with DCM
  2. dry with materialDry the combined organic extracts over anhydrous Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate in vacuo
  5. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (20:1, 10:1 and 5:1)

Sources & evidence

ORD record
ord-d935193f552743a0986baade419bbecb
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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