Ethylene Glycol → Methyl 1,4-dioxa-8-azaspiro[4.5]decane-6-carboxylate

HRID 479812

Reaction equation

HRID 479812 reaction equation
CC1C=CC(S(O)(=O)=O)=CC=1.[CH2:12]([OH:15])[CH2:13][OH:14].Cl.[CH3:17][O:18][C:19]([CH:21]1[C:26](=O)[CH2:25][CH2:24][NH:23][CH2:22]1)=[O:20]>C1C=CC=CC=1>[NH3:23].[CH3:17][O:18][C:19]([CH:21]1[CH2:22][NH:23][CH2:24][CH2:25][C:26]21[O:15][CH2:12][CH2:13][O:14]2)=[O:20]

Participants

6

Reactant 3

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 2724028Methyl 4-oxopiperidine-3-carboxylate hydrochloride

Product 2

HCID 222AmmoniaHCID 20598088Methyl 1,4-dioxa-8-azaspiro[4.5]decane-6-carboxylateYield 127.7%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

PTSA (24.7, 130 mmol) and ethylene glycol (24.8 mL, 439 mmol) were added to methyl-4-oxo-3-piperidine carboxylate hydrochloride (90) (25.1 g, 130 mmol) in benzene (52 mL, 2.5 M). The solution was stirred and heated to reflux overnight. H2O was removed using a Dean Stark trap. When the reaction was judged complete by TLC, 5% aqueous NaHCO3 and CH2Cl2 were added, and the organic layer was removed. The aqueous layer was extracted with CH2Cl2 (5×), and the combined organics were dried over sodium sulfate, filtered and concentrated in vacuo, and purified by silica gel chromatography with 20:1 CH2Cl2:2N NH3 in EtOH to provide 91 (16.7 g, 64%). 1H NMR (CDCl3) 3.82-3.70 (4H, m), 3.48 (3H, s), 3.00-2.50 (4H, m), 2.43 (1H, t), 1.76 (1H, m), 1.30 (1H, m) ppm. 13C NMR (CDCl3): 171.83, 106.57, 64.34, 64.17, 51.36, 48.91, 46.54, 43.69, 33.97 ppm.

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. customH2O was removed
  4. additionwere added
  5. customthe organic layer was removed
  6. extractionThe aqueous layer was extracted with CH2Cl2 (5×)
  7. dry with materialthe combined organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel chromatography with 20:1 CH2Cl2

Sources & evidence

ORD record
ord-44c260cdf40c453f926b2bb096247334
Source dataset
uspto-grants-2003_11
Patent number
US06645980B1

Linked notes

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