2-Methyl-3-butyn-2-ol → 2-Methyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-but-3-yn-2-ol

HRID 1984647Notes

Reaction equation

HRID 1984647 reaction equation
I[C:2]1[C:3]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:4][O:5][C:6]=1[CH3:7].C(N(CC)CC)C.[CH3:21][C:22]([OH:26])([C:24]#[CH:25])[CH3:23]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:21][C:22]([OH:26])([C:24]#[C:25][C:2]1[C:3]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:4][O:5][C:6]=1[CH3:7])[CH3:23]

Participants

7

Reactant 3

HCID 82582-Methyl-3-butyn-2-ol2×HCID 8471Triethylamine2×HCID 27761504-Iodo-5-methyl-3-phenylisoxazole

Product 1

HCID 688532502-Methyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-but-3-yn-2-olYield 78%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalyst2×HCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-iodo-5-methyl-3-phenylisoxazole (5.73 g, 20.1 mmol), palladium(II) acetate (135 mg, 0.60 mmol), 1,3-bis(diphenylphosphino)propane (249 mg, 0.60 mmol), triethylamine (7.0 mL, 50.2 mmol) and 2-methyl-3-butyn-2-ol (3.0 mL, 30.7 mmol) in N,N-dimethylformamide (40 mL) was evaporated and flushed with argon. Cuprous iodide (77 mg, 0.40 mmol) was added and the reaction mixture was stirred for 23 h at 90° C. (after 1.75 h and 4.5 h, respectively, further palladium(II) acetate (135 mg, 0.60 mmol), 1,3-bis(diphenylphosphino)propane (249 mg, 0.60 mmol), triethylamine (7.0 mL, 50.2 mmol), 2-methyl-3-butyn-2-ol (3.0 mL, 30.7 mmol) and cuprous iodide (77 mg, 0.40 mmol) were added) before cooled to ambient temperature and separated between aqueous sodium hydroxide (1 M, 600 mL) and ethyl acetate (1000 mL). The aqueous layer was extracted with ethyl acetate (1000 mL) and washed with aqueous sodium hydroxide (1 M, 600 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate=67:33) afforded the title compound (3.77 g, 78%) as a yellow oil. MS: m/e=242.2 [M+H]+.

Workup

  1. customwas evaporated
  2. customflushed with argon
  3. temperaturebefore cooled to ambient temperature
  4. customseparated between aqueous sodium hydroxide (1 M, 600 mL) and ethyl acetate (1000 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (1000 mL)
  6. washwashed with aqueous sodium hydroxide (1 M, 600 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated
  9. customPurification by chromatography (SiO2, heptane:ethyl acetate=67:33)

Sources & evidence

ORD record
ord-eef96f50c0cd4a6a8e30c86abe2d91d4
Source dataset
uspto-grants-2009_06
Patent number
US07544704B2

Reaction notes

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