Hydrochloric Acid → 3-Methoxy-5-methyl-4-piperidin-1-ylmethylphenol

HRID 1505893Notes

Reaction equation

HRID 1505893 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:16]=[C:15]([O:17]C2CCCCO2)[CH:14]=[C:13]([CH3:24])[C:5]=1[CH2:6][N:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.C(=O)([O-])[O-].[Na+].[Na+]>CO>[CH3:2][O:3][C:4]1[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([CH3:24])[C:5]=1[CH2:6][N:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 582666091-[2-Methoxy-6-methyl-4-(tetrahydropyran-2-yloxy)-benzyl]-piperidine

Product 1

HCID 582664193-Methoxy-5-methyl-4-piperidin-1-ylmethylphenolYield 33.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1N Hydrochloric acid (10 mL) was added to 1-[2-methoxy-6-methyl-4-(tetrahydropyran-2-yloxy)-benzyl]-piperidine (2.33 g, 7.3 mmol) in methanol (30 mL) and the reaction mixture was stirred at ambient temperature for 2 h. The pH of the solution was adjusted to 9 by the addition of saturated aqueous sodium carbonate solution (20 mL) and the aqueous phase was extracted with DCM (3×30 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford a colourless oil. The resultant oil was purified by flash chromatography (silica, 12 g column, ISCO, 0-15% (2N ammonia in MeOH) in DCM) to afford the title compound as a white solid (570 mg, 33%). NMR (CDCl3, 400 MHz): 6.14 (d, J=2.4 Hz, 1H), 5.99 (s, 1H), 3.68 (s, 3H), 3.49 (s, 2H), 2.56-2.46 (m, 4H), 2.25 (s, 3H), 1.65-1.51 (m, 4H), 1.48-1.36 (s, 2H).

Workup

  1. extractionthe aqueous phase was extracted with DCM (3×30 mL)
  2. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customto afford a colourless oil
  6. customThe resultant oil was purified by flash chromatography (silica, 12 g column, ISCO, 0-15% (2N ammonia in MeOH) in DCM)

Sources & evidence

ORD record
ord-df65e32a321c4563a47717d88032f547
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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