Potassium Carbonate → [2-(3-Methoxyphenyl)-3,4-Dihydro-6-methoxynaphthalen-1-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

HRID 481956Notes

Reaction equation

HRID 481956 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)=[O:14])=[C:8]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[CH2:7][CH2:6]2.C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:38][CH2:39][N:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:38][CH2:39][N:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)=[CH:17][CH:16]=1)=[O:14])=[C:8]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 15458258[2-(3-Methoxyphenyl)-3,4-Dihydro-6-methoxynaphthalen-1-yl][4-hydroxyphenyl]methanone

Product 1

HCID 9893303[2-(3-Methoxyphenyl)-3,4-Dihydro-6-methoxynaphthalen-1-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[3,4-dihydro-6-methoxy-2-(3-methoxyphenyl)-1-naphthalenyl](4-hydroxyphenyl)methanone (3.5 g, 9.0 mmol), anhydrous K2CO3 (6.25 g, 45 mmol), N-2-chloroethylpiperidine hydrochloride (1.75 g, 9.5 mmol, Aldrich Chem. Co.) 10 mg of KI, and anhydrous DMF (150 mL) were combined under a nitrogen atmosphere and the resulting mixture was stirred at room temperature for 16 hr. The DMF was removed under reduced pressure and the residue was distributed into water and ethyl acetate. The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. After concentration to an oil, the product was purified by column chromatography over silica gel using a gradient from chloroform to 95:5 chloroform:methanol. The appropriate fractions gave, on evaporation of the solvent and vacuum drying of the residue at 80° C. overnight, an oil which weighed 3.1 g (69%). 1H NMR (CDCl3) d 7.80 (d, J=9.0 Hz, 2H), 7.10-7.00 (m, 1H), 6.90-6.70 (m, 6H), 6.70-6.68 (m, 2H), 4.09 (t, J=5.9 Hz, 2H), 3.78 (s, 3H), 3.65 (s, 3H), 3.02 (t, J=8.1 Hz, 2H), 2.90-2.70 (m, 4H), 2.60-2.40 (m, 3H), 1.70-1.50 (m, 5H), 1.50-1.01 (m, 2H); MS (FD) m/e 497 (M+); Anal. Calc'd. for C32H35NO4 : C, 77.24; H, 7.09; N, 2.82. Found: C, 77.05; H, 7.19; N, 3.05.

Workup

  1. customThe DMF was removed under reduced pressure
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationAfter concentration to an oil
  6. customthe product was purified by column chromatography over silica gel using a gradient from chloroform to 95:5 chloroform
  7. customThe appropriate fractions gave, on evaporation of the solvent and vacuum
  8. customdrying of the residue at 80° C. overnight

Sources & evidence

ORD record
ord-e07a9c55f5764f1ab8daf030048973c1
Source dataset
uspto-grants-1998_08
Patent number
US05792762

Reaction notes

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