Diisopropylethylamine → 3-(2-Methyl-5-nitrophenyl)furan

HRID 2070352Notes

Reaction equation

HRID 2070352 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[CH3:8].ClC1C=CC(NC2N(C)C3C=CC(O[C:31]4C=CN=[C:33]([C:37](NC)=[O:38])[CH:32]=4)=CC=3N=2)=CC=1[N+]([O-])=O.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.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].C(Cl)Cl>[CH3:8][C:7]1[CH:6]=[CH:5][C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]=1[C:33]1[CH:32]=[CH:31][O:38][CH:37]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 821892-Bromo-4-nitrotolueneHCID 131730050HCID 131730050, compound

Product 1

HCID 600980813-(2-Methyl-5-nitrophenyl)furanYield 80%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 3-bromo-4-methyl nitrobenzene 1 (421 mg, 2.0 mmol), 3-furan boronic acid 2 (452 mg, 4.0 mmol), diisopropylethylamine (1.4 mL, 8.0 mmol), and Pd(dppf)Cl2—CH2Cl2 (162 mg, 0.2 mmol) in dry NMP (10 mL) was sparged with Ar for 20 min. The reaction mixture was heated to 80° C. and maintained at that temperature for 16 h. The reaction was allowed to cool to rt and was then partitioned with water and EtOAc. The resulting mixture was filtered through Celite and the phases partitioned and separated. The aqueous portion was extracted with EtOAc (3×) and the combined organic phases were washed with brine, dried (MgSO4), and concentrated. The crude residue was adsorbed onto SiO2 and purified by flash chromatography (9:1 hexanes-EtOAc) to furnish 319 mg (1.57 mmol, 80%) of an off-white solid as 3: 1H NMR (300 MHz, CD3OD) δ 8.16 (d, J=2.5 Hz, 1H), 8.04 (dd, J=2.5, 8.5 Hz, 1H), 7.77 (dd, J=0.8, 1.7 Hz, 1H), 7.63 (app t, J=1.9 Hz, 1H), 7.48 (d, J=8.5 Hz, 1H), 6.72 (dd, J=0.8, 1.9 Hz, 1H), 2.48 (s, 3H).

Workup

  1. customwas sparged with Ar for 20 min
  2. temperaturemaintained at that temperature for 16 h
  3. temperatureto cool to rt
  4. customwas then partitioned with water and EtOAc
  5. filtrationThe resulting mixture was filtered through Celite
  6. customthe phases partitioned
  7. customseparated
  8. extractionThe aqueous portion was extracted with EtOAc (3×)
  9. washthe combined organic phases were washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated
  12. custompurified by flash chromatography (9:1 hexanes-EtOAc)

Sources & evidence

ORD record
ord-f4bffc2530fc475aa55394b8d6f51be8
Source dataset
uspto-grants-2012_10
Patent number
US08299108B2

Reaction notes

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