Cesium fluoride → [6-Hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513920Notes

Reaction equation

HRID 1513920 reaction equation
CS([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:19][CH:18]=1)=[C:11](OS(C(F)(F)F)(=O)=O)[CH:10]=[CH:9]2)(=O)=O.[F-].[Cs+].B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.Br[C:60]1[CH:65]=[C:64]([F:66])[CH:63]=[C:62]([F:67])[C:61]=1[F:68]>C(#N)C>[OH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([C:16]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]3)=[CH:19][CH:18]=1)=[O:32])=[C:11]([C:60]1[CH:65]=[C:64]([F:66])[CH:63]=[C:62]([F:67])[C:61]=1[F:68])[CH:10]=[CH:9]2

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 2734316Bis(neopentyl glycolato)diboronHCID 27363991-Bromo-2,3,5-trifluorobenzeneHCID 11628623Trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

Product 1

HCID 11237470[6-Hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 100.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

Dissolve trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (10.0 g, 16.6 mmol) in degassed acetonitrile (100 mL). Add cesium fluoride (13.0 g, 83 mmol) and bis(acetato)bis(triphenylphosphine)palladium (1.2 g, 1.7 mmol) followed by bis(neopentyl glycolato)diboron (4.5, 19.9 mmol) and plunge into a 75° C. oil bath under nitrogen. After 15 minutes, add 1-bromo-2,3,5-trifluorobenzene (7.0 g, 33.2 mmol) to the reaction and bis(acetato)bis(triphenylphosphine)palladium (500 mg) and stir at 75° C. for 2.5 hours. Cool the reaction to room temperature and filter through celite. Concentrate the filtrate in vacuo and redissolve the residue in methanol (100 mL). Add KOH (4 g) and stir at room temperature overnight. Pour the reaction into saturated aqueous ammonium chloride and extract with methylene chloride. Dry the organic layer with sodium sulfate, filter and concentrate in vacuo. Purify on 5 SCX columns (loading with methanol and eluting with 2M NH3 in methanol) to obtain 8.4 g (100%) of the title compound. Mass spectrum (ion spray): m/z=506.4 (M+H).

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. filtrationfilter through celite
  4. concentrationConcentrate the filtrate in vacuo
  5. dissolutionredissolve the residue in methanol (100 mL)
  6. stirringAdd KOH (4 g) and stir at room temperature overnight
  7. additionPour
  8. customthe reaction into saturated aqueous ammonium chloride
  9. extractionextract with methylene chloride
  10. dry with materialDry the organic layer with sodium sulfate
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. customPurify on 5 SCX columns (loading with methanol and eluting with 2M NH3 in methanol)

Sources & evidence

ORD record
ord-f23e090161af4c7ba0afc19c70eeca5c
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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