N-Iodosuccinimide → Methyl 4-iodo-5-isobutylisoxazole-3-carboxylate

HRID 1804506Notes

Reaction equation

HRID 1804506 reaction equation
[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:6]=1)[CH:2]([CH3:4])[CH3:3].[I:14]N1C(=O)CCC1=O>FC(F)(F)C(O)=O>[I:14][C:6]1[C:7]([C:10]([O:12][CH3:13])=[O:11])=[N:8][O:9][C:5]=1[CH2:1][CH:2]([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 120273N-IodosuccinimideHCID 3477558Methyl 5-isobutylisoxazole-3-carboxylate

Product 1

HCID 58374143Methyl 4-iodo-5-isobutylisoxazole-3-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A mixture of methyl 5-isobutylisoxazole-3-carboxylate (0.923 g, 5.04 mmol) and N-iodosuccinimide (1.25 g, 5.54 mmol) in trifluoroacetic acid (25 mL) was stirred at room temperature overnight. By HPLC, the reaction was complete. The trifluoroacetic acid was removed under reduced pressure, and the residue was diluted with dichloromethane (100 mL), washed with a saturated aqueous solution of sodium bicarbonate (2×25 mL), washed with a 2.5% aqueous solution of sodium bisulfate (25 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a 5% mixture of ethyl acetate in hexane afforded methyl 4-iodo-5-isobutylisoxazole-3-carboxylate (1.21 g, 3.91 mmol, 78% yield) as a pale yellow oil. The product had an HPLC ret. time=2.40 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=310.1.

Workup

  1. customThe trifluoroacetic acid was removed under reduced pressure
  2. additionthe residue was diluted with dichloromethane (100 mL)
  3. washwashed with a saturated aqueous solution of sodium bicarbonate (2×25 mL)
  4. washwashed with a 2.5% aqueous solution of sodium bisulfate (25 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration under reduced pressure
  7. customfollowed by purification by flash silica gel chromatography

Sources & evidence

ORD record
ord-978a07962a504cfbb6565f4ab3a738cd
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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