2,5-Dihydroxybenzoic acid → 5-(2,6-Dimethyl-4-nitrophenoxy)-2-(2-methoxyethoxymethoxy)benzoic acid 2-methoxyethoxymethyl ester

HRID 1359170Notes

Reaction equation

HRID 1359170 reaction equation
[Na].[H-].[Na+].[OH:4][C:5]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][C:6]=1[C:7]([OH:9])=[O:8].Cl[C:16]1[C:21]([CH3:22])=[CH:20][C:19]([N+:23]([O-:25])=[O:24])=[CH:18][C:17]=1[CH3:26].[CH3:27][O:28][CH2:29][CH2:30][O:31][CH2:32]Cl>CN1C(=O)CCC1.CCOCC>[CH3:27][O:28][CH2:29][CH2:30][O:31][CH2:32][O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:11]([O:14][C:16]2[C:21]([CH3:22])=[CH:20][C:19]([N+:23]([O-:25])=[O:24])=[CH:18][C:17]=2[CH3:26])[CH:12]=[CH:13][C:5]=1[O:4][CH2:27][O:28][CH2:29][CH2:30][O:31][CH3:32]

Participants

7

Reactant 4

HCID 34692,5-Dihydroxybenzoic acidHCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 99205692-Chloro-1,3-dimethyl-5-nitrobenzeneHCID 86584955HCID 86584955, compound

Product 1

HCID 541396135-(2,6-Dimethyl-4-nitrophenoxy)-2-(2-methoxyethoxymethoxy)benzoic acid 2-methoxyethoxymethyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of sodium NaH (60% dispersion in mineral oil; 1.32 g, 33 mmol) in 50 mL of NMP is cooled to 0° C. and 2,5-dihydroxybenzoic acid (1.54 g, 10 mmol) is added in one portion. The mixture is warmed to room temperature, and after 30 min, 4-chloro-3,5-dimethylnitrobenzene (2.41 g, 13 mmol) is added in one portion and the reaction is heated at 120° C. for 3 h. The reaction is cooled to RT and 2-methoxyethoxymethyl chloride (2.85 mL, 25 mmol) is added. After stirring for 30 min, the mixture is poured onto water and the product is taken up in Et2O. The organic solution is washed with brine, dried over anhydrous Na2SO4 and concentrated. Chromatography on silica (eluant; EtOAc/hexane-1/2→3/2) affords 5-(2,6-dimethyl-4-nitrophenoxy)-2-(2-methoxyethoxymethoxy)benzoic acid 2-methoxyethoxymethyl ester: NMR (CDCl3) 2.23 (s, 6H), 3.36 (s, 3H), 3.38 (s, 3H), 3.54-3.60 (m, 4H), 3.80-3.90 (m, 4H), 5.28 (s, 2H), 5.52 (s, 2H), 6.82 (dd, 1H, J=9,3), 7.17-7.23 (m, 2H), 8.02 (s, 2H).

Workup

  1. temperatureThe mixture is warmed to room temperature
  2. temperaturethe reaction is heated at 120° C. for 3 h
  3. temperatureThe reaction is cooled to RT
  4. additionthe mixture is poured onto water
  5. washThe organic solution is washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-342f60cb19bd4a9ea7438ef0bb6a69d9
Source dataset
uspto-grants-2003_07
Patent number
US06599942B1

Reaction notes

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