Nitrogen → N-(2',4'-difluoro-5-nitrobiphenyl-3-yl)acetamide

HRID 64085

Reaction equation

HRID 64085 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:11][C:12](=[O:14])[CH3:13])[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.N#N.[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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]>[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([NH:11][C:12](=[O:14])[CH3:13])[CH:3]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 10658908N-(3-bromo-5-nitrophenyl)acetamide

Product 1

HCID 89500094N-(2',4'-difluoro-5-nitrobiphenyl-3-yl)acetamideYield 80%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of N-(3-bromo-5-nitrophenyl)acetamide (1 g, 3.86 mmol) in 1,2-dimethoxyethane (15 ml) was degassed by N2 bubbling for 5 min. 2,4-Difluorophenylboronic acid (0.727 g, 4.63 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.627 g, 0.769 mmol, 0.2 eq.) and aqueous sodium carbonate (1.22 g, 11.5 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5 min and then heated at 90° C. for 2 h. The mixture was quenched with water and extracted with ethyl acetate (3×50 ml). The combined organic layer was washed with water, brine and dried over sodium sulphate. The solvent was distilled off under reduced pressure and the crude residue was purified by column chromatography (60-120 silica gel, 30% ethyl acetate in hexane) to give the product in 80% yield (0.9 g). 1H NMR (300 MHz, DMSO-d6): δ 10.63 (s, 1H), 8.7-8.69 (m, 1H), 8.16 (d, 1H), 8.04 (s, 1H), 7.8-7.67 (m, 1H), 7.53 (m, 1H), 7.34 (m, 1H), 2.19 (s, 3H).

Workup

  1. customthe mixture was degassed for another 5 min
  2. customthe mixture was further degassed for 5 min
  3. customThe mixture was quenched with water
  4. extractionextracted with ethyl acetate (3×50 ml)
  5. washThe combined organic layer was washed with water, brine
  6. dry with materialdried over sodium sulphate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe crude residue was purified by column chromatography (60-120 silica gel, 30% ethyl acetate in hexane)
  9. customto give the product in 80% yield (0.9 g)

Sources & evidence

ORD record
ord-e22b3ee5a0c241e38ce9d93b1983acae
Source dataset
uspto-grants-2016_09
Patent number
US09447091B2

Linked notes

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