1,3-Dimethoxybenzene → HCID 21103678, compound

HRID 1354852Notes

Reaction equation

HRID 1354852 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=1>CCOC(C)=O.[Cl-].[Zn+2].[Cl-]>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([O:23][CH3:24])[CH:20]=[CH:21][C:22]=1[C:5]([C:4]1[CH:8]=[CH:9][C:10]([N+:12]([O-:14])=[O:13])=[CH:11][C:3]=1[O:2][CH3:1])=[O:6]

Participants

5

Reactant 2

HCID 90251,3-DimethoxybenzeneHCID 30161132-Methoxy-4-nitrobenzoyl chloride

Product 1

HCID 21103678HCID 21103678, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

2-Methoxy-4-nitro-benzoyl chloride (392) (0.5 g, 2.32 mmol), 1,3-dimethoxy-benzene (393) (0.962 g, 6.96 mmol) and zinc (II) chloride (0.063 g, 0.46 mmol) were combined. The mixture was heated to 150° C. for 30 minutes. TLC indicated product formation. The mixture was diluted with EtOAc (200 mL), washed with aqueous HCl (100 mL, 1.0 M), NaHCO3 (aqueous saturated, 100 mL) and brine (100 mL) via extraction, dried over MgSO4 and concentrated under reduced pressure. Purification by flash chromatography on silica gel using a gradient of hexane and EtOAc (eluting with 15–100% EtOAc/hexane in 30 minutes) gave the desired product along with the corresponding o-acylated product (10:1 ratio by NMR). Recrystallization from acetone followed by filtration under reduced pressure gave the desired product (394) as yellow cubic crystals (0.618 g, 2.0 mmol, >99% pure, 84% yield). 1H NMR (400 MHz, Acetone-d6): δ 3.53 (s, 3H), 3.78 (s, 3H), 3.85 (s, 3H), 6.58 (d, 1H, J=2.4 Hz), 6.64 (dd, 1H, J=8.4 Hz, 2 Hz), 7.44 (d, 1H, J=8 Hz), 7.63 (d, 1H, J=9.2 Hz), 7.81 (d, 1H, J=2 Hz), 7.84 (dd, 1H, J1=8.4 Hz, J2=2.4 Hz).

Workup

  1. washwashed with aqueous HCl (100 mL, 1.0 M), NaHCO3 (aqueous saturated, 100 mL) and brine (100 mL) via extraction
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash chromatography on silica gel using a gradient of hexane and EtOAc (eluting with 15–100% EtOAc/hexane in 30 minutes)

Sources & evidence

ORD record
ord-b6f918908a594210bb21bb934985649f
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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