Ethyl bromoacetate → (3R)-tert-butyl 3-((3-chlorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate

HRID 451657Notes

Reaction equation

HRID 451657 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:10]([OH:24])[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)[CH:7]=[CH:8][CH:9]=1.Br[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].[NH4+].[Cl-]>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([CH:10]([O:24][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:12]2)[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59201373(R)-tert-butyl 3-((3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

Product 1

HCID 59201743(3R)-tert-butyl 3-((3-chlorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of NaH (0.608 g, 15.2 mmol) in DMF (60 mL) at 0-5° C. was added dropwise with a solution of (3R)-tert-butyl 3-((3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (4.35 g, 12.68 mmol) in DMF (30 mL). The mixture was stirred for 1 h at rt. A solution of ethyl bromoacetate (2.52 g, 15.2 mmol) in DMF (30 mL) was added dropwise and the mixture was heated to reflux for 3 h. When the reaction was complete, the mixture was poured into satd aq NH4Cl, and extracted with EtOAc (3×100 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give (3R)-tert-butyl 3-((3-chlorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate (2.09 g, 40%). 1H NMR (400 MHz, CDCl3): 1.23-1.27 (m, 3H), 1.43-1.45 (m, 9H), 3.95-3.99 (m, 3H), 4.12-4.17 (m, 4H), 4.32-4.38 (d, 1H), 7.14-7.17 (m, 1H), 7.26-7.28 (m, 3H). MS (E/Z): 412 (M+H+).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3 h
  3. extractionextracted with EtOAc (3×100 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5bb59d136e0948baba06a4d2fbdbc51b
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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