Sodium Bicarbonate → 3-Methyl-5-(1-CBZ-2(S)-pyrrolidinyl)isoxazole

HRID 21763Notes

Reaction equation

HRID 21763 reaction equation
[C:1]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH:16]=[CH:17][C:18](=[N:20][OH:21])[CH3:19])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C([O-])(O)=O.[Na+]>O.C1COCC1.OS([O-])=O.[Na+]>[CH3:19][C:18]1[CH:17]=[C:16]([C@@H:12]2[CH2:13][CH2:14][CH2:15][N:11]2[C:1]([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])[O:21][N:20]=1

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 867487371-(1-CBZ-2(S)-pyrrolidinyl)-1-buten-3-one oxime

Product 1

HCID 109460703-Methyl-5-(1-CBZ-2(S)-pyrrolidinyl)isoxazoleYield 60.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 23665763Sodium BisulfiteSolvent

Procedure

A 169 mg sample (0.59 mmol) of the product from step 23d above, 344 mg (2.07 mmol) of Kl, 156 mg ((0.61. mmol) of 12, and 198 mg (2.36 mmol) of NaHCO3 were dissolved in 3 mL of water and 3 mL of THF. The mixture was heated at reflux for 6 hr, then cooled to room temperature. The mixture was diluted with 20 mL of 1.7 M NaHSO3 solution, then extracted with ether. The combined extracts were washed with brine and dried over MgSO4, then concentrated to give 143 mg of crude product. Chromatography on silica gel, eluting with 20% ethyl acetate in hexane afforded 102 mg of the title compound after removal of the solvent.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 6 hr
  3. extractionextracted with ether
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto give 143 mg of crude product
  8. washChromatography on silica gel, eluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-b25a8f120a90430d9a460f8222478dff
Source dataset
uspto-grants-1995_06
Patent number
US05424444

Reaction notes

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