Water → 4-Cyclopropyl-2-fluoro-1-nitrobenzene

HRID 1185256Notes

Reaction equation

HRID 1185256 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]([F:16])[CH:8]=1)(=O)=O.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:19]1([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]([F:16])[CH:8]=2)[CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 962WaterHCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 2760897Cyclopropylboronic acidHCID 219987353-Fluoro-4-nitrophenyl trifluoromethanesulfonate

Product 1

HCID 574239144-Cyclopropyl-2-fluoro-1-nitrobenzeneYield 91.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-fluoro-4-nitrophenyl trifluoromethanesulfonate (7.15 g, 24.73 mmol), cyclopropylboronic acid (2.55 g, 29.67 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complexed with dichloromethane (1:1) (1.62 g, 1.98 mmol), and 2M cesium carbonate in water (19.8 mL, 39.56 mmol) in toluene (39.5 mL) was degassed for 20 min. The reaction mixture was stirred at 90° C. under N2 for 2.5 h. The reaction was cooled to RT, diluted with ethyl acetate (200 mL), and filtered through a pad of Celite. The filtrate was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified via flash column chromatography eluted with 0 to 75% DCM/hexane to give 4.11 g (91.7%) of 4-cyclopropyl-2-fluoro-1-nitrobenzene as an oil. 1H NMR (400 MHz, MeOD) δ 7.98 (dd, J=10.2, 6.6 Hz, 1H), 7.12-7.02 (m, 2H), 2.11-1.97 (m, 1H), 1.20-1.11 (m, 2H), 0.89-0.82 (m, 2H).

Workup

  1. customwas degassed for 20 min
  2. temperatureThe reaction was cooled to RT
  3. additiondiluted with ethyl acetate (200 mL)
  4. filtrationfiltered through a pad of Celite
  5. washThe filtrate was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified via flash column chromatography
  10. washeluted with 0 to 75% DCM/hexane

Sources & evidence

ORD record
ord-a1635af6c8074d88a7f52fb8601296ec
Source dataset
uspto-grants-2014_03
Patent number
US08669361B2

Reaction notes

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