Triethylamine → 5-(4-Benzyloxy-benzenesulfonyl)-2-oxa-5-aza-bicyclo[2.2.2]octan-3-one

HRID 2269310Notes

Reaction equation

HRID 2269310 reaction equation
C[O:2][C:3]([CH:5]1[CH2:10][C:9](=O)[CH2:8][CH2:7][N:6]1C(OC(C)(C)C)=O)=[O:4].[BH4-].[Na+].C(N(CC)CC)C.[CH2:28]([O:35][C:36]1[CH:41]=[CH:40][C:39]([S:42](Cl)(=[O:44])=[O:43])=[CH:38][CH:37]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CO.C(OCC)(=O)C.Cl>[CH2:28]([O:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([N:6]2[CH2:7][CH:8]3[CH2:9][CH2:10][CH:5]2[C:3](=[O:2])[O:4]3)(=[O:44])=[O:43])=[CH:38][CH:37]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 47383854-(Benzyloxy)benzene-1-sulfonyl chlorideHCID 104002141-tert-Butyl 2-methyl 4-oxopiperidine-1,2-dicarboxylate

Product 1

HCID 183337695-(4-Benzyloxy-benzenesulfonyl)-2-oxa-5-aza-bicyclo[2.2.2]octan-3-oneYield 29.5%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-oxo-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.1 g, 3.9 mmol) in 20 mL of methanol was added sodium borohydride (0.14 9, 3.9 mmol) at 0° C. After stirring for 2 h at 0° C., the mixture was diluted with ethyl acetate, washed with 1M HCl, 1M NaOH, and brine, dried over Na2SO4, filtered and concentrated. The residue was taken up in 10 mL of 6M aqueous HCl and was refluxed for 4 h. After cooling to room temperature, the mixture was concentrated in vacuo, and the residue was dissolved in 5.5 mL of anhydrous DMF. The solution was cooled to 0° C. and was treated with triethylamine (4.8 mL, 34 mmol) and 4-benzyloxy-benzenesulfonyl chloride (2.5 g, 8.8 mmol). After stirring for 2 h, the mixture was diluted with 1M HCl, extracted 3× with ethyl acetate, and the organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane, affording 0.43 g of 5-(4-benzyloxy-benzenesulfonyl)-2-oxa-5-aza-bicyclo[2.2.2]octan-3one as a colorless solid.

Workup

  1. washwashed with 1M HCl, 1M NaOH, and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. temperaturewas refluxed for 4 h
  6. temperatureAfter cooling to room temperature
  7. concentrationthe mixture was concentrated in vacuo
  8. dissolutionthe residue was dissolved in 5.5 mL of anhydrous DMF
  9. temperatureThe solution was cooled to 0° C.
  10. stirringAfter stirring for 2 h
  11. extractionextracted 3× with ethyl acetate
  12. dry with materialthe organic layers were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. filtrationThe residue was filtered through a small pad of silica gel eluting with 1:1 ethyl acetate-hexane

Sources & evidence

ORD record
ord-8501e25f0b7947a9be57e42cd425b387
Source dataset
uspto-grants-2001_12
Patent number
US06329397B1

Reaction notes

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