Cesium carbonate → 4-Cyclopropyl-2-fluoro-1-nitrobenzene

HRID 79004

Reaction equation

HRID 79004 reaction equation
[F:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH:19]1(B(O)O)[CH2:21][CH2:20]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH:19]1([C:4]2[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([F:1])[CH:3]=2)[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2760897Cyclopropylboronic acidHCID 219987353-Fluoro-4-nitrophenyl trifluoromethanesulfonate

Product 1

HCID 574239144-Cyclopropyl-2-fluoro-1-nitrobenzeneYield 81.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A stirred suspension of trifluoro-methanesulfonic acid 3-fluoro-4-nitro-phenyl ester (5.6 g, 19 mmol), cyclopropyl boronic acid (2.09 g, 23.3 mmol) Pd(dppf)Cl2 (1.24 g, 1.5 mmol) and 2M aqueous cesium carbonate (30 mL, 60 mmol) in toluene (20 mL) was degassed before being heated at 90° C. under an argon atmosphere for 2.5 hours. The reaction mixture was allowed to cool to room temperature before filtering through a pad of Celite®, washing with ethyl acetate. The filtrate was washed (water, brine), and then dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-30% ethyl acetate in pentane) to give the title compound as a yellow solid (2.79 g, 81%). 1H NMR (DMSO-d6, 400 MHz) 8.03 (1 H, t, J=8.39 Hz), 7.28 (1 H, dd, J=13.19, 1.91 Hz), 7.16 (1 H, dd, J=8.61, 1.90 Hz), 2.14-2.05 (1 H, m), 1.21-1.05 (2 H, m), 0.92-0.82 (2 H, m).

Workup

  1. customwas degassed
  2. temperatureto cool to room temperature
  3. filtrationbefore filtering through a pad of Celite®
  4. washwashing with ethyl acetate
  5. washThe filtrate was washed (water, brine)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bcebc5a0d9714a5d9ad3123f096d0406
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Linked notes

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