Sodium hydride → (R)-1-(2-(2-benzylbenzyloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester

HRID 1451497

Reaction equation

HRID 1451497 reaction equation
[H-].[Na+].[CH2:3]([C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH2:12][OH:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br.[CH2:19]([O:21][C:22]([C@@H:24]1[CH2:29][CH2:28][CH2:27][N:26]([CH2:30][CH2:31]Br)[CH2:25]1)=[O:23])[CH3:20]>C1COCC1>[CH2:19]([O:21][C:22]([C@@H:24]1[CH2:29][CH2:28][CH2:27][N:26]([CH2:30][CH2:31][O:13][CH2:12][C:11]2[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=2[CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:25]1)=[O:23])[CH3:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 741092-Benzylbenzyl alcoholHCID 70009171(R)-1-(2-bromoethyl)nipecotic acid ethyl ester hydrobromide

Product 1

HCID 54112458(R)-1-(2-(2-benzylbenzyloxy)ethyl)-3-piperidinecarboxylic acid ethyl esterYield 8.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (2.1 g, 53 mmol, 60% oil dispersion) was added portionwise to a stirred solution of 2-benzylbenzylalcohol (5.0 g, 25 mmol) in dry THF (125 ml) placed under an atmosphere of nitrogen. The mixture was heated at reflux for 1 h and then allowed to cool to ambient temperature within 30 minutes. (R)-1-(2-Bromoethyl)-3-piperidinecarboxylic acid ethyl ester hydrobromide (8.6 g, 25 mmol, EP 374801) was added and the mixture was stirred for 2 days at ambient temperature. The reaction mixture was diluted with THF (100 ml) and filtered. The solvent was evaporated in vacuo to give an oily residue which was purified by column chromatography (700 g, heptane/ethyl acetate=1/1) to give 0.8 g of (R)-1-(2-(2-benzylbenzyloxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. filtrationfiltered
  4. customThe solvent was evaporated in vacuo
  5. customto give an oily residue which
  6. customwas purified by column chromatography (700 g, heptane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-d6f6c692759448d6b8358f840d6520db
Source dataset
uspto-grants-1997_02
Patent number
US05604242

Linked notes

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