Potassium Carbonate → 1-(4-Amino-3-methoxyphenyl)piperidin-4-ol

HRID 1014194Notes

Reaction equation

HRID 1014194 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[C:4]([O:11][CH3:12])[CH:3]=1.[OH:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([N:17]2[CH2:18][CH2:19][CH:14]([OH:13])[CH2:15][CH2:16]2)=[CH:3][C:4]=1[O:11][CH3:12]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 79341Piperidin-4-olHCID 27792505-Fluoro-2-nitroanisole

Product 1

HCID 573534601-(4-Amino-3-methoxyphenyl)piperidin-4-olYield 63%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A solution of 4-fluoro-2-(methyloxy)-1-nitrobenzene (3.0 g, 17.5 mmol), 4-hydroxypiperidine (1.77 g, 17.5 mmol) and potassium carbonate (2.9 g, 21 mmol) in DMSO was stirred for 24 h. The reaction was diluted with water and extracted three times with Ethyl acetate. The combined organic solutions were dried over MgSO4 and concentrated. The resulting residue was stirred in ethanol and acetic acid with 10% Pd/C under 30 psi of hydrogen for 16 hr. The reaction was filtered through a pad of celite, rinsed with Ethyl acetate. The filtrate was concentrated and dissolved in methylene chloride. The organic solution was washed with saturated sodium bicarbonate, dried over MgSO4, and concentrated to give 1-[4-amino-3-(methyloxy)phenyl]-4-piperidinol (2.44 g, 63% yield over 2 steps). 1H NMR (400 MHz, d6-DMSO) δ 6.49-6.45 (m, 2H), 6.27 (dd, J=8.4 and 2.4 Hz, 1H), 4.60 (d, J=4.0 Hz, 1 H), 4.18 (s, 2H), 3.71 (s, 3H), 3.54-3.48 (m, 1H), 3.25-3.22 (m, 2H), 2.63-2.56 (M, 2H), 1.80-1.76 (m, 2H), 1.51-1.42 (m, 2H).

Workup

  1. extractionextracted three times with Ethyl acetate
  2. dry with materialThe combined organic solutions were dried over MgSO4
  3. concentrationconcentrated
  4. filtrationThe reaction was filtered through a pad of celite
  5. washrinsed with Ethyl acetate
  6. concentrationThe filtrate was concentrated
  7. dissolutiondissolved in methylene chloride
  8. washThe organic solution was washed with saturated sodium bicarbonate
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b33ef526b01d4d2686d331f438668f1b
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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