Ethyl Acetate → 4-(2-Oxoethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

HRID 1027388Notes

Reaction equation

HRID 1027388 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH2:19][CH:20]=C)[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2].CC[O:24]C(C)=O>CC(O)C.O.O=[Os](=O)(=O)=O>[CH2:1]([O:3][C:4]([C:6]1([CH2:19][CH:20]=[O:24])[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

6

Reactant 2

HCID 8857Ethyl AcetateHCID 162182701-tert-Butyl 4-ethyl 4-(prop-2-en-1-yl)piperidine-1,4-dicarboxylate

Product 1

HCID 584784234-(2-Oxoethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl esterYield 34%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

4-Allyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (2.97 g, 10 mmol) was dissolved in iPrOH (50 mL) and H2O (10 mL). To this was added a aqueous solution of NaIO4 (4.68 g, 21.8 mmol) in water (40 mL), followed by addition of OsO4 (8.4 mg, crystals, in one portion) at rt. The solution was stirred at rt. After 30 min, milky cloudy formed. Stirring was continued overnight. TLC and LC/MS did not detect the SM, but it was still very milky. The reaction mixture was poured into ice water (20 mL) and EtOAc (30 mL). The two layers were separated and the aqueous layer was extracted with EtOAc (3×15 mL). The combined extracts were washed with brine, and concentrated to dryness to obtain a liquid. The liquid was subject to a distillation under reduced pressure to remove isopropanol. The remaining liquid was purified on a 50 g silica gel column, eluted with MeOH in DCM (0-5%). Note: the product is not UV active. Anisaldehyde visualization was used. The product fractions were collected and concentrated to yield 1.03 g (34% yield) of the title compound as a liquid.

Workup

  1. custommilky cloudy formed
  2. stirringStirring
  3. waitwas continued overnight
  4. customThe two layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  6. washThe combined extracts were washed with brine
  7. concentrationconcentrated to dryness
  8. customto obtain a liquid
  9. distillationThe liquid was subject to a distillation under reduced pressure
  10. customto remove isopropanol
  11. customThe remaining liquid was purified on a 50 g silica gel column
  12. washeluted with MeOH in DCM (0-5%)
  13. customThe product fractions were collected
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-05924f6f472c495abcf3d29d9bb9c267
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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