2-Bromopyridine → Ethyl 5-(pyridin-2-yl)isoxazole-3-carboxylate

HRID 1951934Notes

Reaction equation

HRID 1951934 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:13]1[O:17][N:16]=[C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:14]=1)CCC.F[P-](F)(F)(F)(F)F.C([N+]1C=CN(C)C=1)CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:13]1[O:17][N:16]=[C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:14]=1

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 27341741-Butyl-3-methylimidazolium hexafluorophosphateHCID 2763256Ethyl 5-(tributylstannyl)-1,2-oxazole-3-carboxylate

Product 1

HCID 23006229Ethyl 5-(pyridin-2-yl)isoxazole-3-carboxylateYield 43%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 20 mL BIOTAGE® microwave vial and stir bar were oven dried and cooled under a stream of dry nitrogen. The vial was flushed with argon and charged with dichlorobis(triphenylphosphine)-palladium(II) (96 mg, 0.137 mmol) and dioxane (12 mL) followed by sparging with argon for several minutes. 2-Bromopyridine (0.217 mL, 2.28 mmol), ethyl 5-(tributylstannyl)isoxazole-3-carboxylate (980 mg, 2.28 mmol), and 1-butyl-3-methylimidazolium hexafluorophosphate (0.047 mL, 0.228 mmol) were added and sparging was continued for several minutes. The vial was sealed and processed in a BIOTAGE® microwave at 150° C. for 60 minutes. The solution was cooled, evaporated, and the residue was loaded onto a 120 g Isco silica gel cartridge, which was pre-equilibrated with hexanes, and then eluted with 0-50% EtOAc/Hexanes. The product fractions were evaporated to give a pale yellow oil, which solidified after being placed under high vacuum to afford ethyl 5-(pyridin-2-yl)isoxazole-3-carboxylate (212 mg, 0.972 mmol, 43% yield). The product had an HPLC retention. time=2.48 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=219.1. 1H NMR (400 MHz, chloroform-d) δ ppm 1.42-1.48 (m, 3H), 4.49 (q, J=7.28 Hz, 2H), 7.31 (s, 1H), 7.39 (ddd, J=7.53, 4.89, 1.13 Hz, 1H), 7.87 (td, J=7.78, 1.76 Hz, 1H), 7.96 (d, J=7.78 Hz, 1H), and 8.73 (d, 1H).

Workup

  1. customdried
  2. temperaturecooled under a stream of dry nitrogen
  3. customThe vial was flushed with argon
  4. customby sparging with argon for several minutes
  5. customsparging
  6. waitwas continued for several minutes
  7. customThe vial was sealed
  8. temperatureThe solution was cooled
  9. customevaporated
  10. washeluted with 0-50% EtOAc/Hexanes
  11. customThe product fractions were evaporated
  12. customto give a pale yellow oil, which

Sources & evidence

ORD record
ord-b2ea9ee5b3984f71a9b2c7872c5f90ac
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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