Ethyl bromoacetate → 4-[4-(3-Ethoxycarbonyl-2-pyridin-2-yl-propionyl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2042575Notes

Reaction equation

HRID 2042575 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:31])[CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)=[CH:19][CH:18]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35]>CS(C)=O.C1(C)C=CC=CC=1>[C:3]([O:7][C:8]([N:10]1[CH2:11][CH2:12][CH:13]([O:16][C:17]2[CH:18]=[CH:19][C:20]([C:23](=[O:31])[CH:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:21][CH:22]=2)[CH2:14][CH2:15]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 59651881HCID 59651881, compound

Product 1

HCID 596520014-[4-(3-Ethoxycarbonyl-2-pyridin-2-yl-propionyl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl esterYield 94%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 1140TolueneSolvent

Procedure

A mixture of sodium hydride (0.21 g, 8.8 mmoL) in 10 mL of DMSO was stirred under N2 as 4-[4-(2-pyridine-2-yl-acetyl)-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (3.50 g, 8.83 mmol) in 15 mL of DMSO was added dropwise. After 30 min, a solution of ethyl bromoacetate (1.47 g, 8.83 mmol) in 8.0 mL of toluene was added dropwise. The reaction was stirred at rt for 2 h and then quenched with saturated NH4Cl solution, and the solvent was evaporated. The residue was extracted with CH2Cl2 (3×20 mL), combined, washed with saturated NaHCO3, saturated NaCl solution and dried over Na2SO4. The crude product was purified by Combiflash chromatography (CH2Cl2 to 1% MeOH in CH2Cl2) to give the product (4.0 g, 94%): Mp 118-120° C.; MS m/z 483 (M+H).

Workup

  1. additionwas added dropwise
  2. customquenched with saturated NH4Cl solution
  3. customthe solvent was evaporated
  4. extractionThe residue was extracted with CH2Cl2 (3×20 mL)
  5. washwashed with saturated NaHCO3, saturated NaCl solution
  6. dry with materialdried over Na2SO4
  7. customThe crude product was purified by Combiflash chromatography (CH2Cl2 to 1% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-756a49ebb78841b1853d5164880a7d8c
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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