Tris(furan-2-yl)phosphane → 5-(3-(3-Hydroxy-propyl)-phenyl)-isoxazole-3-carboxylic Acid Ethyl Ester

HRID 1375665Notes

Reaction equation

HRID 1375665 reaction equation
I[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[CH2:28]([O:30][C:31]([C:33]1[CH:37]=[C:36]([Sn](CCCC)(CCCC)CCCC)[O:35][N:34]=1)=[O:32])[CH3:29].[F-].[K+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I.C(OCC)C>[CH2:28]([O:30][C:31]([C:33]1[CH:37]=[C:36]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH2:9][CH2:10][OH:11])[CH:3]=2)[O:35][N:34]=1)=[O:32])[CH3:29]

Participants

9

Reactant 4

HCID 521585Tris(furan-2-yl)phosphaneHCID 522689Potassium FluorideHCID 2763256Ethyl 5-(tributylstannyl)-1,2-oxazole-3-carboxylateHCID 15169851Benzenepropanol, 3-iodo-

Product 1

HCID 695081845-(3-(3-Hydroxy-propyl)-phenyl)-isoxazole-3-carboxylic Acid Ethyl EsterYield 61.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

To 3-(3-iodophenyl)-1-propanol (1.55 g, 5.60 mmol), tri-2-furylphosphine (130 mg, 0.56 mmol), tris(dibenzylideneacetone)dipalladium (256 mg, 0.23 mmol), and CuI (107 mg, 0.56 mmol) was added DMF (10 mL). To this mixture was added a solution of 5-tributylstannanyl-isoxazole-3-carboxylic acid ethyl ester (2.41 g, 5.60 mmol) as a solution in DMF (10 mL). The reaction was stirred under N2 at ambient temperature for 1 hour, then 5% (w/v) KF(aq) (100 mL) and diethyl ether (50 mL)were added. The biphasic mixture was stirred vigorously for 10 minutes, then filtered through diatomaceous earth to remove the solid precipitates. The precipitate was washed with diethyl ether to recover any organic material from the filter pad, then the combined filtrate and washings were separated. The aqueous layer was extracted with additional ether (2×25 ML), the combined ether layers were washed with water (1×25 mL), and brine (1×25 mL), dried over MgSO4, filtered, and concentrated to an oil. The product was purified via silica gel chromatography, eluting with 40% ethyl acetate/hexanes to provide the titled compound (950 mg, 2%). 1H NMR (500 MHz, d6-DMSO) δ 7.81 (s, 1H), 7.77 (d, 1H, J=7.5 Hz), 7.47 (t, 1H, J=7.6 Hz), 7.47 (s, 1H), 7.39 (d, 1H, J=7.4 Hz), 4.49 (t, 1H, J=5.2 Hz), 4.41 (q, 2H, J=7.2 Hz), 3.44 (q, 2H, J=5.9 Hz), 2.71 (t, 2H, J=7.8 Hz), 1.78 (m, 2H), 1.36 (t, 3H, J=7.2 Hz); MS (ESI) m/z 276 (M+H)+, 293 (M+NH4)+, 298 (M+Na)+.

Workup

  1. stirringThe biphasic mixture was stirred vigorously for 10 minutes
  2. filtrationfiltered through diatomaceous earth
  3. customto remove the solid
  4. customprecipitates
  5. washThe precipitate was washed with diethyl ether
  6. customto recover any organic material from the filter pad
  7. customthe combined filtrate and washings were separated
  8. extractionThe aqueous layer was extracted with additional ether (2×25 ML)
  9. washthe combined ether layers were washed with water (1×25 mL), and brine (1×25 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated to an oil
  13. customThe product was purified via silica gel chromatography
  14. washeluting with 40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2c584c4d6bd9492c8c25ba1cce8ec760
Source dataset
uspto-grants-2007_01
Patent number
US07169797B2

Reaction notes

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