Potassium Acetate → 3-(4-Hept-1-ynyl-isoxazol-3-yl)-pyridine

HRID 660187Notes

Reaction equation

HRID 660187 reaction equation
Br[C:2]1[C:3]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:4][O:5][CH:6]=1.[C:13]([Si](C)(C)C)#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].CC([O-])=O.[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[C:13]([C:2]1[C:3]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:4][O:5][CH:6]=1)#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]

Participants

8

Reactant 4

HCID 517044Potassium AcetateHCID 2724141Tetrabutylammonium FluorideHCID 10964922Hept-1-ynyl-trimethyl-silaneHCID 575480413-(4-Bromo-1,2-oxazol-3-yl)pyridine

Product 1

HCID 575480553-(4-Hept-1-ynyl-isoxazol-3-yl)-pyridineYield 30%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To anhydrous DMF (20 ml) containing compound 64 (1.08 g, 4.8 mmol), were added 1.5 eq of hept-1-ynyl-trimethyl-silane (1.21 g), 3 eq of KOAc (1.41 g) and 1 eq of TBAF (1.0 M in THF). The resulting mixture was stirred for another 2 hours under N2. Successively were added 10 mol % of Pd(OAc)2 (108 mg) and 20 mol % of PPH3 (251 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-Hept-1-ynyl-isoxazol-3-yl)-pyridine (69A) as an oil (0.34 g, 30%). 1H-NMR (400 MHz, CDCl3): δ 9.3 (d, J=2 Hz, 1H), 8.7 (dd, J=5 Hz, 2 Hz, 1H), 8.58 (s, 1H), 8.34 (dt, J=8 Hz, 2 Hz, 1H), 7.44-7.39 (m, 1H), 2.42 (t, J=7 Hz, 2H), 1.65-1.57 (m, 2H), 1.45-1.29 (m, 4H), 0.91 (t, J=7 Hz, 3H).

Workup

  1. additionAfter the addition
  2. temperatureAfter cooling to room temperature
  3. washwashed three times with a saturated NaHCO3 solution
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Sources & evidence

ORD record
ord-fa62fa429f0742419e9db11d84c5e356
Source dataset
uspto-grants-2011_12
Patent number
US08084473B2

Reaction notes

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