Piperidine → 3-Methoxy-4-piperidin-1-ylmethylphenol

HRID 1888419Notes

Reaction equation

HRID 1888419 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([O:10][CH3:11])[CH:3]=1.[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:11][O:10][C:4]1[CH:3]=[C:2]([OH:1])[CH:9]=[CH:8][C:5]=1[CH2:6][N:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 5195414-Hydroxy-2-MethoxybenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 582667373-Methoxy-4-piperidin-1-ylmethylphenolYield 30.8%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a pre-stirred solution of 4-hydroxy-2-methoxybenzaldehyde (1.02 g, 6.7 mmol), titanium isopropoxide (2.14 mL, 7.0 mmol) and piperidine (0.70 mL, 7.0 mmol) in DCM (20 mL) was added sodium triacetoxyborohydride (2.84 g, 13.4 mmol) in portions. After 3 h the reaction mixture was quenched by the addition of methanol (1.0 mL) and then the solvents were removed under reduced pressure to afford a residue. The resultant residue was then loaded onto an SCX-2 cartridge (10 g) and eluted with 2N ammonia in methanol to afford the title compound (456 mg, 30%). 1H NMR (CD3OD, 300 MHz): 7.17 (d, J=8.3 Hz, 1H), 6.51 (d, J=2.3 Hz, 1H), 6.43 (dd, J=8.2, 2.2 Hz, 1H), 4.07 (s, 2H), 3.84 (s, 3H), 3.16-2.99 (m, 4H), 1.84-1.73 (m, 4H), 1.67-1.56 (m, 2H).

Workup

  1. customAfter 3 h the reaction mixture was quenched by the addition of methanol (1.0 mL)
  2. customthe solvents were removed under reduced pressure
  3. customto afford a residue
  4. washeluted with 2N ammonia in methanol

Sources & evidence

ORD record
ord-9e1a85a3804a4073a6ed3521f3130e95
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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