Triethylamine → 2-(5-Methyl-3-phenyl-isoxazol-4-ylethynyl)-pyridine

HRID 1984640

Reaction equation

HRID 1984640 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].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[C:50]([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=1)#[CH:51]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:7][C:6]1[O:5][N:4]=[C:3]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]=1[C:51]#[C:50][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 137268EthynylpyridineHCID 27761504-Iodo-5-methyl-3-phenylisoxazole

Product 1

HCID 247844462-(5-Methyl-3-phenyl-isoxazol-4-ylethynyl)-pyridineYield 23.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-iodo-5-methyl-3-phenylisoxazole (285 mg, 1.00 mmol), palladium(II) acetate (7 mg, 0.03 mmol), 1,3-bis(diphenylphosphino)propane (12 mg, 0.03 mmol), triethylamine (348 μL, 2.50 mmol) and 2-ethynylpyridine (131 μL, 1.30 mmol) in N,N-dimethylformamide (2 mL) was evaporated and flushed with argon. Cuprous iodide (4 mg, 0.02 mmol) was added and the reaction mixture was stirred for 3 h at 90° C. before cooling to ambient temperature and separated between aqueous sodium hydroxide (1 M, 30 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL) and washed with aqueous sodium hydroxide (1 M, 30 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 67:33) afforded the title compound (60 mg, 23%) as a light brown solid. MS: m/e=261.2 [M+H]+.

Workup

  1. customwas evaporated
  2. customflushed with argon
  3. temperaturebefore cooling to ambient temperature
  4. customseparated between aqueous sodium hydroxide (1 M, 30 mL) and ethyl acetate (50 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
  6. washwashed with aqueous sodium hydroxide (1 M, 30 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated
  9. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 67:33)

Sources & evidence

ORD record
ord-cfb5c6edebff49b29fea7c3ae5467541
Source dataset
uspto-grants-2009_06
Patent number
US07544704B2

Linked notes

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