Hydrochloric Acid → tert-Butyl 3-(benzyloxy)-4,4-dimethoxypiperidine-1-carboxylate

HRID 1425025Notes

Reaction equation

HRID 1425025 reaction equation
[H-].[Na+].[OH:3][CH:4]1[C:9]([O:12][CH3:13])([O:10][CH3:11])[CH2:8][CH2:7][N:6]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5]1.[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl>CN(C=O)C>[CH2:21]([O:3][CH:4]1[C:9]([O:10][CH3:11])([O:12][CH3:13])[CH2:8][CH2:7][N:6]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 11425480Tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate

Product 1

HCID 67505617tert-Butyl 3-(benzyloxy)-4,4-dimethoxypiperidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (55% content, 0.79 g, 18 mmol) was added to a solution of tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate (described in Tetrahedron Lett.; 46; 3; 2005; 447-450, 3.9 g, 15 mmol) in DMF (50 mL). Following stirring at room temperature for 30 minutes, benzyl bromide (2.82 g, 16.5 mmol) was added, and the mixture was stirred at room temperature for two hours. A 0.5 N aqueous hydrochloric acid solution was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with water (three times) and brine, and dried over anhydrous magnesium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=10/1, 4/1, 2/1) to obtain 4.99 g of the title compound as a colorless solid (95%).

Workup

  1. stirringthe mixture was stirred at room temperature for two hours
  2. extractionfollowed by extraction with ethyl acetate
  3. washThen, the organic layer was washed with water (three times) and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentration under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=10/1, 4/1, 2/1)

Sources & evidence

ORD record
ord-deec2f7355e94b63a4ee574f32e9f10f
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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