Triethylamine → 5-(3-(3-Oxo-butyl)-phenyl)-isoxazole-3-carboxylic Acid Methyl Ester

HRID 1375655Notes

Reaction equation

HRID 1375655 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=2)[O:7][N:6]=1)=[O:4].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:39][CH:40]([OH:43])[CH:41]=[CH2:42].C(N(CC)CC)C>CN(C)C=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH2:42][CH2:41][C:40](=[O:43])[CH3:39])[CH:11]=2)[O:7][N:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 117163-Buten-2-olHCID 80271Tri-o-tolylphosphineHCID 53393795Methyl 5-(3-bromophenyl)isoxazole-3-carboxylate

Product 1

HCID 695080965-(3-(3-Oxo-butyl)-phenyl)-isoxazole-3-carboxylic Acid Methyl EsterYield 59.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 5-(3-Bromo-phenyl)-isoxazole-3-carboxylic acid methyl ester (1.5 g, 5.3 mmol), Pd(OAc)2 (60 mg, 0.27 mmol), P(o-tolyl)3 (162 mg, 0.53 mmol) in anhydrous N,N-dimethylformamide (15 mL) in a pressure tube was added 3-buten-2-ol (0.92 mL, 10.6 mmol) and triethylamine (1.1 mL, 7.95 mmol). The mixture was flushed with nitrogen for 3 minutes, capped and heated to 100° C. for 30 minutes. The reaction mixture was allowed to cool to ambient temperature, partitioned between ethyl acetate and water (75 mL, 1:1). The organic layer was washed with brine (2×25 mL), dried (Na2SO4), filtered, concentrated under reduced pressure and purified on a Silica Gel MPLC eluting with 20–40% ethyl acetate/hexanes to provide the titled compound as a light yellow solid (860 mg, 59%). MS (ESI(+)) m/e 274 (M+H)+.

Workup

  1. customThe mixture was flushed with nitrogen for 3 minutes
  2. customcapped
  3. temperatureto cool to ambient temperature
  4. custompartitioned between ethyl acetate and water (75 mL, 1:1)
  5. washThe organic layer was washed with brine (2×25 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. custompurified on a Silica Gel MPLC
  10. washeluting with 20–40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-93c2b8de9d8549a5bef97182f8516e1d
Source dataset
uspto-grants-2007_01
Patent number
US07169797B2

Reaction notes

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