Tetrahydrofuran → 3-(4-Hex-1-enyl-isoxazol-3-yl)-pyridine

HRID 1027559Notes

Reaction equation

HRID 1027559 reaction equation
C1COCC1.Br[C:7]1[C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:9][O:10][CH:11]=1.[CH:18](/B(O)O)=[CH:19]\[CH2:20][CH2:21][CH2:22][CH3:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[CH:18]([C:7]1[C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:9][O:10][CH:11]=1)=[CH:19][CH2:20][CH2:21][CH2:22][CH3:23]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 5326225B-(1E)-1-Hexenylboronic acidHCID 575480413-(4-Bromo-1,2-oxazol-3-yl)pyridine

Product 1

HCID 672853663-(4-Hex-1-enyl-isoxazol-3-yl)-pyridineYield 72.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To anhydrous THF (30 ml) containing compound 64 (0.64 g, 2.84 mmol), were added 1.5 eq of (E)-hexene-1-ylboronic acid (0.55 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.2 g), 2 mol % of Pd(OAc)2 (13 mg) and 4 mol % of S-Phos (47 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed 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-hex-1-enyl-isoxazol-3-yl)-pyridine (compound 67A) as an oil (0.47 g, 69%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 8.0 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.41 (m, 1H), 6.11-5.99 (m, 2H), 2.22-2.14 (m, 2H), 1.46-1.29 (m, 4H), 0.91 (t, J=7 Hz, 3H).

Workup

  1. additionAfter the addition
  2. temperatureAfter cooling to room temperature
  3. washwashed 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-4b01c5f677cb4c2d8096eaac39310d0e
Source dataset
uspto-grants-2014_05
Patent number
US08735388B2

Reaction notes

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