Acetic Acid → 1-Boc-4-Piperidin-1-ylmethyl-piperidine

HRID 419346Notes

Reaction equation

HRID 419346 reaction equation
[CH:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)=O.CC(O)=O.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[N:20]1([CH2:1][CH:3]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 8082PiperidineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 539146451-Boc-4-Piperidin-1-ylmethyl-piperidineYield 93%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To 1,1-dimethylethyl 4-formyl-1-piperidinecarboxylate (1.02 g, 4.78 mmol) in 1,2-dichloroethane (50 mL) was added sequentially, HOAc (6.00 mL, 1M in DCM, 6.00 mmol), piperidine (1.0 mL, 10.1 mmol) and sodium triacetoxyborohydride (1.60 g, 7.55 mmol). The reaction was stirred at rt for 2 hours at which time HOAc (1.00 mL, 1M in DCM, 1.00 mmol) and sodium triacetoxyborohydride was added. When complete by TLC the reaction was quenched with saturated NaHCO3 (150 mL) and extracted with DCM. The combined organic layer was washed with H2O, dried (MgSO4) and concentrated to provide the title compound (1.25 g, 4.43 mmol, 93%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80-0.91 (m, 2H), 1.29-1.35 (m, 11H), 1.38-1.46 (m, 4H), 1.59 (d, J=10.6 Hz, 3H), 2.00 (d, J=6.8 Hz, 2H), 2.21 (br. s., 4H), 2.62 (br. s., 2H), 3.85 (d, J=12.6 Hz, 2H).

Workup

  1. additionwas added
  2. customWhen complete by TLC the reaction was quenched with saturated NaHCO3 (150 mL)
  3. extractionextracted with DCM
  4. washThe combined organic layer was washed with H2O
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ca60045c72384154b34ca71c2d0674fc
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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