Piperidine → 1-[2-Methoxy-6-methyl-4-(tetrahydropyran-2-yloxy)-benzyl]-piperidine

HRID 1888429Notes

Reaction equation

HRID 1888429 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH:8]=[C:7]([CH3:18])[C:4]=1[CH:5]=O.[NH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH:8]=[C:7]([CH3:18])[C:4]=1[CH2:5][N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 107531782-Methoxy-4-(2-tetrahydropyranyl)oxy-6-methylbenzaldehyde

Product 1

HCID 582666091-[2-Methoxy-6-methyl-4-(tetrahydropyran-2-yloxy)-benzyl]-piperidineYield 101.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a pre-stirred solution of 2-methoxy-6-methyl-4-(tetrahydropyran-2-yloxy)-benzaldehyde (2.14 g, 8.6 mmol) and piperidine (0.93 mL, 9.4 mmol) in DCM (35 mL) at 0° C. was added sodium triacetoxyborohydride (2.72 g, 12.8 mmol) in portions. The reaction mixture was allowed to warm to ambient temperature and then partitioned between water (30 mL) and ethyl acetate (75 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford the title compound as a colourless oil (2.78 g, quantitiative yield) that was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz): 6.51 (d, J=2.4 Hz, 1H), 6.45 (d, J=2.4 Hz, 1H), 5.40 (t, J=3.3 Hz, 1H), 3.98-3.88 (m, 1H), 3.76 (s, 3H), 3.64-3.55 (m, 1H), 3.39 (s, 2H), 2.42-2.27 (m, 7H), 2.07-1.93 (m, 1H), 1.90-1.77 (m, 2H), 1.75-1.52 (m, 3H), 1.54-1.44 (m, 4H), 1.43-1.34 (m, 2H).

Workup

  1. custompartitioned between water (30 mL) and ethyl acetate (75 mL)
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-cd4c2dc7f61e4ca89473889f98c7599e
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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