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

HRID 1513905Notes

Reaction equation

HRID 1513905 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:39][C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=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>[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]=3[C:44]3[CH:45]=[C:40]([F:39])[CH:41]=[CH:42][C:43]=3[F:46])=[O:16])=[CH:13][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 57552509Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester

Product 1

HCID 57552524[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,5-difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-methanoneYield 93%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

Dissolve trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester (2.00 g, 3.63 mmol) in 5 mL of degassed acetonitrile and add 2,5-difluorophenyl boronic acid (1.15 g, 7.26 mmol), trans[dichlorobis(triphenylphosphine)]palladium II (0.51 g, 0.73 mmol) and sonicate briefly. Next add cesium fluoride (4.96 g, 32.76 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 give 1.74 g (93%) of 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-d4725476df134cc7bf22a5c1d2126b3b
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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