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

HRID 1513954Notes

Reaction equation

HRID 1513954 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.F[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[C:40]=1B(O)O.[F-:49].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:49][C:44]1[CH:43]=[CH:42][C:41]([F:45])=[CH:40][C:39]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]=1[C:13]([C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:18][CH:19]=1)=[O:29]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 27343362,6-Difluorophenylboronic acidHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

Product 1

HCID 57552548[2-(2,5-Difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

Add trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (552 mg, 1.0 mmol), 2,6-difluorophenyl boronic acid (320 mg, 2.0 mmol), trans dichlorobis(triphenylphosphine)palladium II (70 mg, 0.1 mmol) and cesium fluoride (1.3 g, 8.6 mmol) to a 20 mL vial along with 8.0 mL degassed acetonitrile. Seal the vial with a septum and purge with nitrogen gas. Heat the mixture with stirring at 80° C. for three hours. Cool, filter and purify on an SCX column, eluting with 2N ammonia/methanol. The compound is further purified on a silica gel column, eluting with a 0-5% 2N ammonia in methanol/methylene chloride gradient. The yield is 260 mg (50%).

Workup

  1. customdegassed acetonitrile
  2. customSeal the vial with a septum
  3. custompurge with nitrogen gas
  4. temperatureHeat the mixture
  5. temperatureCool
  6. filtrationfilter
  7. custompurify on an SCX column
  8. washeluting with 2N ammonia/methanol
  9. customThe compound is further purified on a silica gel column
  10. washeluting with a 0-5% 2N ammonia in methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-954ad1d7dc40409688dd2243f456ef7b
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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