Triethylamine → (2-Cyano-6-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl ester

HRID 352211Notes

Reaction equation

HRID 352211 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[C:3]=1[C:9]1[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:12]([CH3:19])[O:11][N:10]=1.C[CH2:21][N:22](CC)CC.[Si](C#N)(C)(C)C>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:17]([O:16][C:14]([C:13]1[C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[C:21]#[N:22])=[N:10][O:11][C:12]=1[CH3:19])=[O:15])[CH3:18]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 82115Trimethylsilyl cyanideHCID 227138064-Ethoxycarbonyl-5-methyl-3-(2-iodo-6-fluoro-phenyl)isoxazole

Product 1

HCID 69848562(2-Cyano-6-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a mixture of ethyl 3-(2-Fluoro-6-iodo-phenyl)-5-methyl-isoxazole-4-carboxylate (0.25 g, 0.67 mmol), tetrakis(triphenylphosphine)palladium (0.08 g, 0.067 mmol), and Et3N (5 mL) under N2 was added TMSCN and heated at reflux overnight. The reaction was cooled to room temperature, diluted with H2O, and extracted with EtOAc (2×). The combined extracts were washed (H2O then brine), dried (MgSO4), filtered, and concentrated. Flash chromatography (silica gel, EtOAc/hexanes gradient) gave the title compound (0.15 g, 82%). Mass Spectrum (ES+) (m/z) 275.0 [M+1].

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. extractionextracted with EtOAc (2×)
  4. washThe combined extracts were washed (H2O
  5. dry with materialbrine), dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7fbb71eb92a14dc4a8d0ae9e1ddbcbcd
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

Loading…