Ethylene Glycol → Benzyl 1,4-dioxa-7-azaspiro[4.4]nonane-7-carboxylate

HRID 597837Notes

Reaction equation

HRID 597837 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.[CH2:17](O)[CH2:18][OH:19]>C1C=CC=CC=1.CCOC(C)=O.CC1C=CC(S(O)(=O)=O)=CC=1.O>[O:19]1[C:2]2([CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])[CH2:3]2)[O:1][CH2:17][CH2:18]1

Participants

6

Reactant 2

HCID 174Ethylene GlycolHCID 5612031-N-Cbz-3-pyrrolidinone

Product 1

HCID 15165037Benzyl 1,4-dioxa-7-azaspiro[4.4]nonane-7-carboxylateYield 101.4%

Reagents, catalysts & solvents 3

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 241BenzeneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of benzyl 3-oxopyrrolidine-1-carboxylate (11.2 g, 51.09 mmol), ethylene glycol (2.4 g, 38.67 mmol) and TsOH.H2O (10 mg) in benzene (100 mL) was heated at reflux using Dean-Stork condenser. After 20 h, the reaction mixture was cooled, diluted with EtOAc (100 mL), washed with water (2×25 mL), brine (25 mL), dried (MgSO4), filtered and concentrated to give yellow oil. Flash column chromatography purification on silica gel column with 1:4 followed by 3:7 EtOAc:hexanes provided desired product (10.32 g, 100%) as colorless liquid. 1H NMR (500 MHz, CDCl3) δ: 7.38-7.28 (5H, m), 5.13 (2H, s), 3.99-3.92 (4H, m), 3.58-3.54 (2H, m), 3.45 (2H, d, J=10.7 Hz), 2.07-2.02 (2H, m).

Workup

  1. temperatureat reflux
  2. temperaturethe reaction mixture was cooled
  3. washwashed with water (2×25 mL), brine (25 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give yellow oil
  8. customFlash column chromatography purification on silica gel column with 1:4

Sources & evidence

ORD record
ord-4d3dafde7f144866bfe196a2dd1a3621
Source dataset
uspto-grants-2011_03
Patent number
US07897593B2

Reaction notes

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