Triphenylphosphine → HCID 86622785, compound

HRID 1965985Notes

Reaction equation

HRID 1965985 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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:46]([NH:49][C:50]([CH:52]1[CH2:56][CH2:55][CH2:54][CH2:53]1)=[O:51])[C:47]#[CH:48]>C(N(CC)CC)C.CN(C=O)C.CCOC(C)=O.CCCCCC.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].[Cu]I>[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:48]#[C:47][CH2:46][NH:49][C:50]([CH:52]1[CH2:56][CH2:55][CH2:54][CH2:53]1)=[O:51]

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 17901248HCID 17901248, compoundHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 86622785HCID 86622785, compoundYield 49,844.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 21226206Ethyl acetate hexaneSolventHCID 22056947triethylamine N,N-dimethylformamideSolvent

Procedure

Dissolve 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1 g, 2.35 mmol), tris(dibenzylideneacetone)-dipalladium(0) (0.03 equiv.), copper(I) iodide (0.06 equiv.) and triphenylphosphine (0.25 equiv.) in triethylamine/DMF (3:1, 4 mL). Stir the mixture for 5 min at ambient temperature, add N-prop-2-ynyl-cyclopentylcarboxamide (430 mg, 2.82 mmol) and heat at 70° C. for 18 h in a sealed tube. Cool the reaction mixture to ambient temperature, dilute with EtOAc/hexane (1:1) and wash with water. Dry the organic fraction over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1 to 7:3) to obtain 7-chloro-6-[3-(cyclopentanecarbonyl-amino)-prop-1-ynyl]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (500 g, 50%).

Workup

  1. temperatureheat at 70° C. for 18 h in a sealed tube
  2. temperatureCool the reaction mixture to ambient temperature
  3. washwash with water
  4. dry with materialDry the organic fraction over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (10:1 to 7:3)

Sources & evidence

ORD record
ord-0afe5a134a174ebf977c1e8f8bef724d
Source dataset
uspto-grants-2013_04
Patent number
US08420631B2

Reaction notes

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