1,4-Dioxane hydrochloride → (R)-1-(4-((3-(3-amino-1-hydroxypropyl)phenoxy)methyl)piperidin-1-yl)ethanone

HRID 2277052Notes

Reaction equation

HRID 2277052 reaction equation
Cl.O1CCOCC1.[C:8]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][O:18][C:19]2[CH:20]=[C:21]([C@H:25]([OH:36])[CH2:26][CH2:27][NH:28]C(=O)OC(C)(C)C)[CH:22]=[CH:23][CH:24]=2)[CH2:13][CH2:12]1)(=[O:10])[CH3:9]>C(Cl)Cl>[NH2:28][CH2:27][CH2:26][C@H:25]([C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][CH:22]=1)[O:18][CH2:17][CH:14]1[CH2:15][CH2:16][N:11]([C:8](=[O:10])[CH3:9])[CH2:12][CH2:13]1)[OH:36]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 131733438(R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate

Product 1

HCID 86271672(R)-1-(4-((3-(3-amino-1-hydroxypropyl)phenoxy)methyl)piperidin-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HCl/dioxane (4M, 2 mL) was added to a solution of (R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate (0.60 g, 1.40 mmol) in CH2Cl2 (10 mL) at 0° C. and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure to give after purification by triturating in diethyl ether Example 11 hydrochloride as a white solid. Yield (0.40 g, 88%); 1H NMR (400 MHz, DMSO-d6); δ 7.18 (t, J=7.8 Hz, 1H), 6.84 (d, J=7.6 Hz, 2H), 6.75 (d, J=7.6 Hz, 1H), 4.60 (t, J=6.4 Hz, 1H), 4.38 (d, J=14.8 Hz, 1H), 4.11 (s, 2H), 3.79 (d, J=6 Hz, 3H), 3.02 (t, J=11.2, 1H), 2.64 (d, J=3.2 Hz, 2H), 2.54 (s, 1H), 1.97 (s, 4H), 1.76 (t, J=16.0 Hz, 2H), 1.66-1.61 (m, 2H), 1.26-1.04 (m, 2H); MS: m/z 307.01 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give
  3. customafter purification
  4. customby triturating in diethyl ether Example 11 hydrochloride as a white solid
  5. customYield (0.40 g, 88%)

Sources & evidence

ORD record
ord-c15d508091bc49c1b4d910cfc360ca63
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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