Cesium fluoride → [6-Benzyloxy-2-(2-fluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513886Notes

Reaction equation

HRID 1513886 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]([C:19](=[O:35])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:22][CH:21]=1)=[C:14](OS(C(F)(F)F)(=O)=O)[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1B(O)O.[F-].[Cs+]>C(#N)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]([C:19]([C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:24][CH:25]=1)=[O:35])=[C:14]([C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=1[F:44])[CH:13]=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 27343542-Fluorophenylboronic acidHCID 57552555Trifluoromethanesulfonic acid 6-benzyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

Product 1

HCID 11444357[6-Benzyloxy-2-(2-fluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 60.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Dissolve trifluoromethanesulfonic acid 6-benzyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (1.00 g, 1.63 mmoles) in 20 ml of acetonitrile and add 2-fluorobenzene boronic acid (0.46 g, 3.26 mmol), trans[dichlorobis(triphenylphosphine)]palladium II (0.23 gm., 0.33 mmoles) and sonicate briefly. Next add cesium fluoride (2.23 g, 14.67 mmol) and heat to 75° C. for one hour. Add Celite and filter. Concentrate the solvent under vacuum, dissolve in methanol and purify on an SCX cartridge, eluting with 2N ammonia/methanol. Further purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient to isolate 550 mg of the title compound (60%).

Workup

  1. customsonicate briefly
  2. filtrationAdd Celite and filter
  3. concentrationConcentrate the solvent under vacuum
  4. dissolutiondissolve in methanol
  5. custompurify on an SCX cartridge
  6. washeluting with 2N ammonia/methanol
  7. customFurther purify on a silica gel column
  8. washeluting with a 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-782db2b8b0dd4b1bb0f1723928bd8c63
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…