Hydrochloric Acid → 1-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-(4-hydroxy-phenyl)-propan-2-one hydrochloride

HRID 1419899Notes

Reaction equation

HRID 1419899 reaction equation
[CH2:1]([C:8]1([OH:32])[CH2:13][CH2:12][N:11]([CH2:14][C:15](=[O:31])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][Si](C(C)(C)C)(C)C)=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[ClH:51]>C1COCC1.CO>[ClH:51].[CH2:1]([C:8]1([OH:32])[CH2:9][CH2:10][N:11]([CH2:14][C:15](=[O:31])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2724141Tetrabutylammonium FluorideHCID 700483361-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propan-2-one

Product 1

HCID 700462401-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-(4-hydroxy-phenyl)-propan-2-one hydrochlorideYield 36%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propan-2-one (0.400 g, 0.88 mmol) was dissolved in THF (4 ml) and stirred for 16 hours at room temperature in the presence of 1N tetra-n-butylammonium fluoride (1 ml, 1 mmol). The reaction mixture was quenched with 20% NH4Cl (15 ml) and the aqueous phase was extracted with ethyl acetate (3×20 ml). Combined organic phases were dried over Na2SO4 and concentrated. The residue was chromatographed over silica gel (ethyl acetate) to give a yellow oil which was dissolved in MeOH (2 ml) and treated with 1N HCl (0.5 ml). The solution was concentrated, the residue was dissolved in isopropanol (i-PrOH) and ether was added to provide 1-(4-Benzyl-4-hydroxy-piperidin-1-yl)-3-(4-hydroxy-phenyl)-propan-2-one hydrochloride (0.120 g, 36%) as white solid, m.p. 180°-181° C. and MS: m/e=340.3 (M+H+).

Workup

  1. customThe reaction mixture was quenched with 20% NH4Cl (15 ml)
  2. extractionthe aqueous phase was extracted with ethyl acetate (3×20 ml)
  3. dry with materialCombined organic phases were dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed over silica gel (ethyl acetate)
  6. customto give a yellow oil which
  7. concentrationThe solution was concentrated
  8. dissolutionthe residue was dissolved in isopropanol (i-PrOH)
  9. additionether was added

Sources & evidence

ORD record
ord-5bda48d684a94275aa362087d7a3f9bc
Source dataset
uspto-grants-1999_03
Patent number
US05889026

Reaction notes

Loading…