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

HRID 1513900Notes

Reaction equation

HRID 1513900 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][CH:43]=[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:41]3[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=3[F:39])=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 27343542-Fluorophenylboronic acidHCID 57552509Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-benzoyl]-6-methoxynaphthalen-2-yl ester

Product 1

HCID 57552551[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2-fluoro-phenyl)-6-methoxy-naphthalen-1-yl]methanoneYield 72.5%

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 (1.68 g, 3.05 mmol) in 30 mL of acetonitrile and add 2-fluorobenzene boronic acid (0.85 g, 6.10 mmol), trans[dichlorobis(triphenylphosphine)]palladium II (0.43 g, 0.61 mmol) and sonicate briefly. Next add cesium fluoride (4.17 g, 27.45 mmol) and heat to 75° C. for 1 hour. Add Celite and filter. Concentrate the solvent under vacuum, dissolve in methanol and purify on an SCX cartridge, eluting with 2 N ammonia/methanol. Purify further on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient to isolate 1.10 g of the title compound (72%).

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 2 N ammonia/methanol
  7. customPurify further on a silica gel column
  8. washeluting with a 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-a803705fab5349ebba7ce56833294aba
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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