Hydrochloric Acid → (3R,4R)-4-(4-hydroxy-phenyl)-piperidin-3-ol hydrochloride

HRID 1507227Notes

Reaction equation

HRID 1507227 reaction equation
[OH:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[ClH:22]>CO.O1CCOCC1>[ClH:22].[OH:14][C:11]1[CH:12]=[CH:13][C:8]([C@H:7]2[CH2:6][CH2:5][NH:4][CH2:3][C@@H:2]2[OH:1])=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 11483231(3R,4R)-tert-Butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 20677893(3R,4R)-4-(4-hydroxy-phenyl)-piperidin-3-ol hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (3R,4R)-tert-butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate (1.5 g, 5.1 mmol, E-2 from example 46 step E) in methanol (50 mL) under nitrogen was added 12.8 mL of 4 M HCl in dioxane and the reaction was stirred for 1 h at rt. The mixture was then evaporated under reduced pressure to dryness and the residue was washed twice with 20 mL of diethyl ether. The solid residue was dried under vacuum to give (3R,4R)-4-(4-hydroxyphenyl)-piperidin-3-ol hydrochloride E-2a (950 mg, 4.1 mmol). LCMS (method F) RT: 0.17 min, m/z 194 (M+H+). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.74-1.93 (m, 2H) 2.61-2.68 (m, 1H) 2.81-2.93 (m, 1H) 3.21-3.33 (m, 2H) 3.78-3.90 (m, 1H) 6.72 (d, J=8.53 Hz, 2H) 7.00 (d, J=8.53 Hz, 2H) 9.14-9.25 (m, 1H) 9.27-9.44 (m, 1H).

Workup

  1. customThe mixture was then evaporated under reduced pressure to dryness
  2. washthe residue was washed twice with 20 mL of diethyl ether
  3. customThe solid residue was dried under vacuum

Sources & evidence

ORD record
ord-e4b1fe571ef747ceabb0b20c9fc59135
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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