Ether hydrochloride → HCID 70046803, compound

HRID 1419897Notes

Reaction equation

HRID 1419897 reaction equation
[CH2:1]([C:8]1([OH:33])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][Si](C(C)(C)C)(C)C)=[CH:21][CH:20]=2)=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[ClH:40].CCOCC>C1COCC1.CO>[ClH:40].[CH2:1]([C:8]1([OH:33])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10953452Ether hydrochlorideHCID 21226445Aluminium lithium hydrideHCID 70048638HCID 70048638, compound

Product 1

HCID 70046803HCID 70046803, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-(4-Benzyl-4-hydroxy-piperidin-1-yl)-N-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionamide (0.71 g, 1.51 mmol) in THF (4 ml) was added dropwise to a 0° C. suspension of LiAlH4 (0.115 g, 3.02 mmol) in THF (4 ml). The reaction mixture was refluxed during 30 min, cooled to 0° C. and quenched carefully with H2O (5 ml). After dilution with H2O (20 ml), the reaction mixture was treated successively with 2N HCl and sat. NaHCO3. The aqueous phase was extracted with CH2Cl2 (3×10 ml), the combined organic phases were dried over Na2SO4 and concentrated. The residue was chromatographed over silica gel (CH2Cl2 --MeOH 9:1 then 4:1) to give a foam which was dissolved in MeOH and treated with excess HCl/ether. The solution was concentrated and the residue was dissolved with EtOH. Addition of ether provided 4-Benzyl-1-[3-(4-hydroxy-phenylamino)-propyl]-piperidin-4-ol hydrochloride (0.160 g, 26%) as beige solid, m.p. 213°-216° C. and MS: m/e=341.5 (M+H+).

Workup

  1. temperatureThe reaction mixture was refluxed during 30 min
  2. customquenched carefully with H2O (5 ml)
  3. additionAfter dilution with H2O (20 ml), the reaction mixture was treated successively with 2N HCl and sat. NaHCO3
  4. extractionThe aqueous phase was extracted with CH2Cl2 (3×10 ml)
  5. dry with materialthe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was chromatographed over silica gel (CH2Cl2 --MeOH 9:1
  8. custom4:1) to give a foam which
  9. concentrationThe solution was concentrated
  10. dissolutionthe residue was dissolved with EtOH
  11. additionAddition of ether

Sources & evidence

ORD record
ord-943b8ed91ca345c98fc48694caa1e0af
Source dataset
uspto-grants-1999_03
Patent number
US05889026

Reaction notes

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