1,2-Dimethoxyethane → N-(2-nitro-6-(pyridin-4-yl)phenyl)acetamide

HRID 589466Notes

Reaction equation

HRID 589466 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[NH:11][C:12](=[O:14])[CH3:13].CC1(C)C(C)(C)OB([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)O1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[N+:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[C:3]=1[NH:11][C:12](=[O:14])[CH3:13])([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 4643062N-(2-bromo-6-nitrophenyl)acetamide

Product 1

HCID 86701067N-(2-nitro-6-(pyridin-4-yl)phenyl)acetamideYield 55.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A degassed mixture of N-(2-bromo-6-nitrophenyl)acetamide (XCI) (2.59 g, 10 mmol, 1.0 eq), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (XCII) (2.05 g, 10 mmol, 1.3 eq), Na2CO3 (2.12 g, 20 mmol, 2 eq) and Pd(PPh3)4 (1.16 g, 1 mmol, 0.1 eq) in a mixed solvent of DME (30 mL) and H2O (10 mL) was heated to reflux under nitrogen overnight, the mixture was poured onto water (40 ml) and extracted with ethyl acetate (30 mL×3). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo, purification the resultant residue was purified by column chromatography (EtOAc:PE=1:4→100% EtOAc) to afford N-(2-nitro-6-(pyridin-4-yl)phenyl)acetamide (XCIII) (1.42 g, 5.52 mmol, 55% yield) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ ppm 1.92 (s, 3H), 7.46 (d, J=5.6 Hz, 2H), 7.69 (t, J=8 Hz, 1H), 7.80 (dd, J=7.6 Hz, J=1.2 Hz, 1H), 8.06 (dd, J=8 Hz, J=1.6 Hz, 1H), 8.73 (d, J=6 Hz, 2H), 9.96 (s, 1H); ESIMS found for C13H11N3O3 m/z 258 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen overnight
  3. additionthe mixture was poured onto water (40 ml)
  4. extractionextracted with ethyl acetate (30 mL×3)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo, purification the resultant residue
  8. customwas purified by column chromatography (EtOAc:PE=1:4→100% EtOAc)

Sources & evidence

ORD record
ord-68161ad2a6a8435990a1791c4b18e7e4
Source dataset
uspto-grants-2016_01
Patent number
US09233104B2

Reaction notes

Loading…