Cesium fluoride → [4-(2-Azepan-1-yl-ethoxy)-phenyl]-[6-methoxy-2-(2,3,5-trifluorophenyl)-naphthalen-1-yl]-methanone

HRID 1513907Notes

Reaction equation

HRID 1513907 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:38]=[CH:37][C:14]([C:15]([C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=4)[CH:20]=[CH:19][C:18]=3OS(C(F)(F)F)(=O)=O)=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[Cs+].Br[C:42]1[CH:47]=[C:46]([F:48])[CH:45]=[C:44]([F:49])[C:43]=1[F:50]>[Pd].C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Pd].C(#N)C>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:15]([C:17]3[C:26]4[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=4)[CH:20]=[CH:19][C:18]=3[C:42]3[CH:47]=[C:46]([F:48])[CH:45]=[C:44]([F:49])[C:43]=3[F:50])=[O:16])=[CH:37][CH:38]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 27363991-Bromo-2,3,5-trifluorobenzeneHCID 57552509Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester

Product 1

HCID 57552540[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[6-methoxy-2-(2,3,5-trifluorophenyl)-naphthalen-1-yl]-methanoneYield 53.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 2734559Bis(tricyclohexylphosphine) palladium(0)CatalystHCID 6342AcetonitrileSolvent

Procedure

Dissolve trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester (2.60 g, 6.53 mmol) in 200 ml. acetonitrile and add to this bis(pinacoloato)diboron (1.5 g, 7.96 mmol), bis(tricyclohexylphosphine)palladium (0) (0.72 g, 1.50 mmol) and cesium fluoride (7.33 g, 67.0 mmol). Heat the reaction to 100° C. until LC/MS indicates all starting material is consumed. Add to this mixture 1-bromo-2,3,5-trifluorobenzene (2.00 g, 13.06 mmol) and another 720 mg of palladium catalyst and heat at 80° C. for 24 hours. Filter the reaction, concentrate and purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient to give 1.85 g (53%) of the title compound.

Workup

  1. temperatureHeat
  2. customthe reaction to 100° C. until LC/MS
  3. customis consumed
  4. filtrationFilter
  5. customthe reaction
  6. concentrationconcentrate
  7. custompurify on a silica gel column
  8. washeluting with a 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-38477b9ea97944d7a06dc2ab81e1a775
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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