Chloroform → 2-(5-Cyano-2-fluoro-benzoyl)-cyclopropanecarboxylic acid ethyl ester

HRID 1836651Notes

Reaction equation

HRID 1836651 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][C:3]=1B(O)O.[CH2:13]([O:15][C:16]([CH:18]1[CH2:20][CH:19]1[C:21](SC1C=CC(C)=CC=1)=[O:22])=[O:17])[CH3:14].C(Cl)(Cl)Cl.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>S1C=CC=C1C([O-])=O.[Cu+2].S1C=CC=C1C([O-])=O.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].O.C1COCC1>[CH2:13]([O:15][C:16]([CH:18]1[CH2:20][CH:19]1[C:21](=[O:22])[C:3]1[CH:4]=[C:5]([C:8]#[N:9])[CH:6]=[CH:7][C:2]=1[F:1])=[O:17])[CH3:14]

Participants

9

Reactant 4

HCID 6212ChloroformHCID 521585Tris(furan-2-yl)phosphaneHCID 27833615-Cyano-2-fluorobenzeneboronic acidHCID 865876872-p-Tolylsulfanylcarbonyl-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 698411172-(5-Cyano-2-fluoro-benzoyl)-cyclopropanecarboxylic acid ethyl esterYield 66.5%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 15171005Copper thiophene-2-carboxylateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-fluoro-5-cyanophenyl boronic acid (3.10 g,18.8 mmol), 2-p-tolylsulfanylcarbonyl-cyclopropanecarboxylic acid ethyl ester (3.30 g, 12.5 mmol), copper thiophene-2-carboxylate (3.58 g, 18.8 mmol), tris(dibenzylideneacetone)-dipalladium(0).CHCl3 adduct (150 mg, 0.14 mmol), and tri-2-furyl phosphine (0.86 mmol) under N2 was added 125 mL anhydrous THF. The reaction was stirred for 4 h, then poured into 500 mL water and extracted with 500 mL Et2O. The organic layer was extracted with 0.1 N HCl, water, saturated NaHCO3, and water. The organic extract was dried over sodium sulfate, concentrated, and purified by flash chromatography on silica gel using ethyl acetate/hexane (0-10%) as the eluent to yield 2-(5-cyano-2-fluoro-benzoyl)-cyclopropanecarboxylic acid ethyl ester (2.17 g, 66%). 1H NMR (500 MHz, CDCl3) 8.09 (1H, dd, J=2.14, 6.41 Hz), 7.83 (1H, m), 7.31(1H, dd, J=8.55, 10.07 Hz), 4.18 (2H, q, J=7.02 Hz), 3.10 (1H, m), 2.42 (1H, m), 1.68 (2H, m), 1.28 (3H, t, J=7.02 Hz). Anal. calcd. for C14H12FNO3: C, 64.36; H, 4.63; N, 5.36. Found: C, 64.62; H, 4.53; N, 5.26.

Workup

  1. extractionextracted with 500 mL Et2O
  2. extractionThe organic layer was extracted with 0.1 N HCl, water, saturated NaHCO3, and water
  3. extractionThe organic extract
  4. dry with materialwas dried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-c9453e1381714c3a991b142e06f47c59
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

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