Sodium hydride → (R)-tert-butyl 3-((R)-1-(2-(tert-butyldimethylsilyloxy)ethoxy)-1-(3-chlorophenyl)ethyl)piperidine-1-carboxylate

HRID 451714Notes

Reaction equation

HRID 451714 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@:8]([C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:27][CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]>C1COCC1>[Si:30]([O:29][CH2:28][CH2:27][O:10][C@:8]([C@@H:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1)([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[CH3:9])([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 59201475(R)-tert-butyl 3-((R)-1-(3-chlorophenyl)-1-hydroxyethyl)piperidine-1-carboxylate

Product 1

HCID 59201381(R)-tert-butyl 3-((R)-1-(2-(tert-butyldimethylsilyloxy)ethoxy)-1-(3-chlorophenyl)ethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (R)-tert-butyl 3-((R)-1-(3-chlorophenyl)-1-hydroxyethyl)piperidine-1-carboxylate (2.5463 g, 7.49 mmol), 60% NaH (2.120 g, 53 mmol), and (2-bromoethoxy)(tert-butyl)dimethylsilane (7.820 g, 32.7 mmol) in THF was heated at 80° C. for 25 h and then cooled to rt. The reaction mixture was then quenched with water and extracted with ethyl acetate (3×), dried over Na2SO4. After the solvent was evaporated under reduced pressure, crude (R)-tert-butyl 3-((R)-1-(2-(tert-butyldimethylsilyloxy)ethoxy)-1-(3-chlorophenyl)ethyl)piperidine-1-carboxylate was used directly in the next step without further purification.

Workup

  1. temperaturecooled to rt
  2. customThe reaction mixture was then quenched with water
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialdried over Na2SO4
  5. customAfter the solvent was evaporated under reduced pressure, crude (R)-tert-butyl 3-((R)-1-(2-(tert-butyldimethylsilyloxy)ethoxy)-1-(3-chlorophenyl)ethyl)piperidine-1-carboxylate
  6. customwas used directly in the next step without further purification

Sources & evidence

ORD record
ord-f455875ebece43e0b9881a1d802ae920
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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