Sodium hydride → Tert-butyl 4-(2-methoxyethoxy)piperidin-1-carboxylate

HRID 2353151Notes

Reaction equation

HRID 2353151 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:17][O:18][CH2:19][CH2:20]Br>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:20][CH2:19][O:18][CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 57476927Tert-butyl 4-(2-methoxyethoxy)piperidin-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Amine preparation: To 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.5 g) in dry DMF (15 mL) was added sodium hydride (447 mg). After stirring for 2 hrs at room temperature, 2-bromoethyl methyl ether (0.7 mL) was added. The reaction mixture was heated to 40° C. overnight, and then diluted with ethyl acetate, washed with water and dried (MgSO4). The solvent was evaporated and the residue purified by flash chromatography to give 4-(2-methoxy-ethoxy)-piperidine-1-carboxylic acid tert-butyl ester (447 mg). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt.

Workup

  1. temperatureThe reaction mixture was heated to 40° C. overnight
  2. washwashed with water
  3. dry with materialdried (MgSO4)
  4. customThe solvent was evaporated
  5. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-e6b59b1da73e41c7ab7ddef6027a42c7
Source dataset
uspto-grants-2010_07
Patent number
US07750002B2

Reaction notes

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