Sodium → HCID 86307969, compound

HRID 1053803Notes

Reaction equation

HRID 1053803 reaction equation
[C:1]1([C@@H:7]([NH:9][CH:10]2[CH:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:14][CH2:13][N:12]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:11]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na]>CCO>[C:1]1([C@@H:7]([NH:9][C@H:10]2[C@H:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:14][CH2:13][N:12]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:11]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 5360545SodiumHCID 118115802HCID 118115802, compound

Product 1

HCID 86307969HCID 86307969, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

The 1-tert-butyl 4-ethyl 3-(((S)-1-phenylethyl)amino)piperidine-1,4-dicarboxylate 5 (8.0 g, 21.2 mmol, 1.0 equiv) was dissolved in dry EtOH (20 mL) under N2. In a separate flame-dried Schlenk flask was placed dry EtOH (150 mL), and sodium (0.450 g, 63.6 mmol, 3.0 equiv) was added portion-wise under N2. The mixture was kept under N2 and vented to remove evolved gases until all of the sodium had dissolved. The clear solution of 1-tert-butyl 4-ethyl 3-(((S)-1-phenylethyl)amino)piperidine-1,4-dicarboxylate was then transferred to the NaOEt solution, and the mixture was stirred at 80° C. under N2 for 16 h. The solvent was removed under in vacuo, and brine (150 mL) was added and the mixture was brought to pH=10 with 1 N NaOH and extracted with EtOAc (100 mL×3). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (silica, petroleum ether/EtOAc=5:1) to give (trans)-1-tert-butyl 4-ethyl 3-(((S)-1-phenylethyl)amino)piperidine-1,4-dicarboxylate 6 as a slight yellow solid (3.7 g, yield: 46%). ESI-MS (M+H)+: 377.2.

Workup

  1. customIn a separate flame-dried Schlenk flask
  2. additionwas added portion-wise under N2
  3. customto remove
  4. dissolutionhad dissolved
  5. customThe solvent was removed under in vacuo, and brine (150 mL)
  6. additionwas added
  7. extractionextracted with EtOAc (100 mL×3)
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (silica, petroleum ether/EtOAc=5:1)

Sources & evidence

ORD record
ord-9af9c1685d5a4124b0be3d048a2e18e5
Source dataset
uspto-grants-2016_07
Patent number
US09394277B2

Reaction notes

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