N-bromobutanimide → Ethyl 4-bromo-5-(pyridin-2-yl)isoxazole-3-carboxylate

HRID 1951935Notes

Reaction equation

HRID 1951935 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:11][N:10]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:8]=1.[Br:17]N1C(=O)CCC1=O>FC(F)(F)C(O)=O.C(OCC)(=O)C>[Br:17][C:8]1[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:10][O:11][C:7]=1[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 23006229Ethyl 5-(pyridin-2-yl)isoxazole-3-carboxylate

Product 1

HCID 23006245Ethyl 4-bromo-5-(pyridin-2-yl)isoxazole-3-carboxylateYield 69.1%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 5-(pyridin-2-yl)isoxazole-3-carboxylate (212 mg, 0.972 mmol) and N-bromosuccinimide (432 mg, 2.43 mmol) in trifluoroacetic acid (6 mL) was heated to 150° C. for 30 minutes via microwave. Concentration under reduced pressure afforded a yellow oil which was diluted with ethyl acetate (80 mL), washed with a saturated aqueous solution of sodium bicarbonate (20 mL), washed with brine (20 mL), and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a 1:3 mixture ethyl acetate and hexane afforded ethyl 4-bromo-5-(pyridin-2-yl)isoxazole-3-carboxylate (0.217 g, 0.672 mmol, 69% yield). The product had an HPLC retention. time=2.65 min.—Column: YMC S5 COMBISCREEN® 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=299.02. 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (t, J=7.15 Hz, 3H), 4.52 (q, J=7.28 Hz, 2H), 7.43-7.48 (m, 1H), 7.90 (td, J=7.78, 1.76 Hz, 1H), 8.11 (d, J=8.03 Hz, 1H), and 8.84 (d, 1H).

Workup

  1. concentrationConcentration under reduced pressure
  2. customafforded a yellow oil which
  3. washwashed with a saturated aqueous solution of sodium bicarbonate (20 mL)
  4. washwashed with brine (20 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-f0a3650177e74dc7b81ced02be5672bb
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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