Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester → [6-Methoxy-2-(2-methoxy-benzyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1830511Notes

Reaction equation

HRID 1830511 reaction equation
[Cl-].[CH3:2][O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][Zn+].[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[C:20]([C:24](=[O:40])[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:27][CH:26]=1)=[C:19](OS(C(F)(F)F)(=O)=O)[CH:18]=[CH:17]2>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CN1C(=O)CCC1.C1COCC1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[C:20]([C:24]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:27][CH:26]=1)=[O:40])=[C:19]([CH2:6][C:5]1[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=1[O:3][CH3:2])[CH:18]=[CH:17]2

Participants

8

Reactant 2

HCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl esterHCID 178489474HCID 178489474, compound

Product 1

HCID 22046618[6-Methoxy-2-(2-methoxy-benzyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 87%

Reagents, catalysts & solvents 5

HCID 67553Tetrabutylammonium IodideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 6344DichloromethaneSolventHCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Procedure

Add a solution of 2-methoxybenzylzinc chloride (8 mL, 0.5 M/THF) to a mixture of trifluoro-methanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (1.0 g, 1.86 mmol), Bu4NI (2.1 g, 5.7 mmol), Pd(dba)2 (68 mg 0.12 mmol) and dppf (66 mg, 0.12 mmol) in NMP/THF (5 mL, 3:2). Heat the mixture to reflux for 2 h. Quench the reaction with water and dilute with CH2Cl2. Wash the organic phase with water and brine, dry over MgSO4, filter and concentrate. Load the crude product on an SCX cartridge, wash with MeOH and elute with 2M NH3/MeOH. Purify the resulting product by flash chromatography (0–5% (2M NH3/MeOH)/CH2Cl2) to afford [6-methoxy-2-(2-methoxy-benzyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (820 mg, 87%).

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux for 2 h
  3. customQuench
  4. customthe reaction with water
  5. washWash the organic phase with water and brine
  6. dry with materialdry over MgSO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. washLoad the crude product on an SCX cartridge, wash with MeOH
  10. washelute with 2M NH3/MeOH
  11. customPurify the resulting product by flash chromatography (0–5% (2M NH3/MeOH)/CH2Cl2)

Sources & evidence

ORD record
ord-078fe69e92d84c5bab3d8f2932dd4e6e
Source dataset
uspto-grants-2006_06
Patent number
US07067510B2

Reaction notes

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