Tetrabutylammonium Fluoride → 1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanone

HRID 2255996Notes

Reaction equation

HRID 2255996 reaction equation
C([Si](C(C)C)(C(C)C)[O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:28])[CH:13]([N:15]2[CH2:20][CH2:19][C:18]([OH:27])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)[CH3:14])=[CH:8][CH:7]=1)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[OH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:28])[CH:13]([N:15]2[CH2:16][CH2:17][C:18]([OH:27])([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:19][CH2:20]2)[CH3:14])=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 102546421-[4-(Triisopropylsilyl)oxylp henyl]-2-(4-hydroxy-4-pheny1piperidino)-1-propanone

Product 1

HCID 152803431-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanoneYield 112.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(4-(Triisopropylsilyloxy)phenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanone (International Application Publication Number: WO 90/14088, Example 36 at page 41; 22.0 g, 45.7 mmol) was dissolved in dry tetrahydrofuran (500 mL). Tetrabutylammonium fluoride (55 ml, 55 mmol, 1N in tetrahydrofuran) was added dropwise to the stirred solution over 3 minutes. After stirring for 1 hour, the reaction mixture was concentrated and the concentrate flash chromatographed on silica gel (3×6 inches). The column was gradiently eluted with ethyl acetate/hexane, then sequentially with 100% ethyl acetate, 1:9 methanol:ethyl acetate and finally with 1:5 methanol:ethyl acetate. Product-containing fractions were stripped to yield 16.7 g (100%) of title product as a light yellow solid which was triturated with hexane; m.p. 95°-97° C.; 1H-NMR (CDCl3) delta (ppm) 8.08 (d, J=8.5 Hz, 2H), 7.48 (d, J=8 Hz, 2H), 7.34 (t, J=8 Hz, 2H), 7.28-7.25 (m, 1H partially obscured by CHCl3 from NMR solvent), 6.89 (d, J=8.5 Hz, 2H), 4.15 (q, J=7 Hz, 1H), 3.0-2.65 (m, 4H), 2.25-2.10 (m, 2H), 1.85-1.77 (m, 2H), 1.35 (d, J=7 Hz, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe concentrate flash chromatographed on silica gel (3×6 inches)
  3. washThe column was gradiently eluted with ethyl acetate/hexane

Sources & evidence

ORD record
ord-c872509f391f4adab67e05fd6679a3e3
Source dataset
uspto-grants-1997_08
Patent number
US05654302

Reaction notes

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