Cesium fluoride → 7-chloro-6-(5-methyl-thiophen-2-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1965974Notes

Reaction equation

HRID 1965974 reaction equation
[F-].[Cs+].[CH3:3][C:4]1[S:8][C:7](B(O)O)=[CH:6][CH:5]=1.[Cl:12][C:13]1[CH:29]=[CH:28][C:16]2[CH2:17][CH2:18][N:19]([C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH2:20][CH2:21][C:15]=2[C:14]=1OS(C(F)(F)F)(=O)=O>COCCOC.CCOC(C)=O>[Cl:12][C:13]1[CH:29]=[CH:28][C:16]2[CH2:17][CH2:18][N:19]([C:22](=[O:27])[C:23]([F:25])([F:26])[F:24])[CH2:20][CH2:21][C:15]=2[C:14]=1[C:7]1[S:8][C:4]([CH3:3])=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 2734374(5-Methylthiophen-2-yl)boronic acidHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 866227817-chloro-6-(5-methyl-thiophen-2-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 70.4%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Add tetrakistriphenylphosphine palladium(0) (27 mg, 0.024 mmol), cesium fluoride (143 mg, 0.942 mmol) and 5-methyl-thiophen-2-yl-boronic acid (134 mg, 0.942 mmol) to a stirred solution of 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (200 mg, 0.471 mmol) in anhydrous DME (8 mL) at room temperature. Heat at 90° C. overnight. Cool the reaction mixture to room temperature, dilute with EtOAc and wash with water. Extract the aqueous phase twice with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 19:1) to obtain 7-chloro-6-(5-methyl-thiophen-2-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (124 mg, 70%).

Workup

  1. temperatureCool the reaction mixture to room temperature
  2. washwash with water
  3. extractionExtract the aqueous phase twice with EtOAc
  4. dry with materialDry the combined organic extracts over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 19:1)

Sources & evidence

ORD record
ord-d40ef56914b64b47a90c28e74f571b2f
Source dataset
uspto-grants-2013_04
Patent number
US08420631B2

Reaction notes

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