Sodium hydride → HCID 131736296, compound

HRID 1053806Notes

Reaction equation

HRID 1053806 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([NH:8][C@H:9]1[C@H:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:12][N:11]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:10]1)=[O:7].[H-].[Na+]>C1COCC1>[O:7]=[C:6]1[CH2:5][CH2:4][CH2:3][CH2:2][N:8]1[C@H:9]1[C@H:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:13][CH2:12][N:11]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:10]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 131736295HCID 131736295, compound

Product 1

HCID 131736296HCID 131736296, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of trans-1-tert-butyl 4-ethyl 3-(5-bromopentanamido)piperidine-1,4-dicarboxylate 8 (3.0 g, 6.9 mmol, 1.0 equiv) in THF (20 mL), NaH (276 mg, 6.9 mmol, 1.0 equiv) was carefully added in small portions at 0° C. The reaction solution was stirred at reflux condition for 4 h. The mixture was quenched with H2O (20 mL), and extracted with EtOAc (30 mL×3). The organic layer was collected, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica, petroleum ether/EtOAc=1:2) to give (trans)-1′-tert-butyl 4′-ethyl 2-oxo-[1,3′-bipiperidine]-1′,4′-dicarboxylate 9 as a slight yellow oil (2.1 g, yield: 88%). ESI-MS (M+H-56)+: 299.1. 1H NMR (400 MHz, CDCl3) δ: 4.10 (q, 4H), 3.38-3.19 (m, 4H), 2.70-2.61 (m, 1H), 2.36-2.31 (m, 2H), 1.95-1.92 (m, 1H), 1.75-1.71 (m, 6H), 1.46 (s, 9H), 1.23 (t, 3H).

Workup

  1. temperatureat reflux condition for 4 h
  2. customThe mixture was quenched with H2O (20 mL)
  3. extractionextracted with EtOAc (30 mL×3)
  4. customThe organic layer was collected
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (silica, petroleum ether/EtOAc=1:2)

Sources & evidence

ORD record
ord-edeffbd427aa48b88f0e6b3f0269f939
Source dataset
uspto-grants-2016_07
Patent number
US09394277B2

Reaction notes

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