Cesium fluoride → 1-(2-{4-[2-(2,4-Difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine

HRID 1513913Notes

Reaction equation

HRID 1513913 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH2:13][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:37][C:38]1[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=1B(O)O.[F-].[Cs+]>C(#N)C.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:37][C:38]1[CH:43]=[C:42]([F:44])[CH:41]=[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[CH2:13][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

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 27343342,4-Difluorophenylboronic acidHCID 57552542Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-yl-ethoxy)-benzyl]-naphthalen-2-yl ester

Product 1

HCID 575525381-(2-{4-[2-(2,4-Difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-yl ester (1.00 g, 1.91 mmol) in 20 mL of degassed acetonitrile and add 2,4-difluorophenyl boronic acid (0.60 g, 3.82 mmol), trans[dichlorobis(triphenylphosphine)]palladium II (0.27 g, 0.38 mmol) and sonicate briefly. Next add cesium fluoride (2.61 g, 17.19 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 to isolate the title compound.

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

Sources & evidence

ORD record
ord-a2a482bc3d1a4321a91d8a5fd1fb10f8
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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