Chloroform → Methyl 5-nitro-2-(2-methoxy-6-methoxymethoxyphenyl)-benzoate

HRID 1358126Notes

Reaction equation

HRID 1358126 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH2:10][O:11][CH3:12])[CH:4]=1.C([Li])CCC.[CH3:18][O:19][C:20](=[O:31])[C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][C:22]=1Br.C(Cl)(Cl)Cl>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[N+:27]([C:25]1[CH:24]=[CH:23][C:22]([C:4]2[C:5]([O:9][CH2:10][O:11][CH3:12])=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])=[C:21]([CH:26]=1)[C:20]([O:19][CH3:18])=[O:31])([O-:29])=[O:28]

Participants

8

Reactant 4

HCID 6212ChloroformHCID 245494Methyl 2-Bromo-5-nitrobenzoateHCID 5426211-Methoxy-3-(methoxymethoxy)benzeneHCID 178418339Butyllithium

Product 1

HCID 18189455Methyl 5-nitro-2-(2-methoxy-6-methoxymethoxyphenyl)-benzoate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 178418476HCID 178418476, compoundSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 1-methoxy-3-methoxymethoxy benzene (3.62 g., 21.55 mmole), prepared as described in J. Med. Chem. 1995, 38, 1437-1445, in THF (15 mL) at −30° C. was treated with n-butyllithium (8.28 ml. of 2.5M in hexane, 20.69 mmole), stirred for 1 hour at 25° C., cooled to 0° C., treated with anhydrous zinc chloride beads (3.5 g, 25.67 mmole), stirred for 2 hours at 25° C., treated with a solution of methyl-2-bromo-5-nitrobenzoate (5.0 g, 19.23 mmol) in THF (20 mL) and bis(triphenylphosphine)palladium dichloride (600 mg), stirred it 65° C. for 15 hours, cooled, and treated with chloroform and aqueous KHCO3. The precipitated zinc salts were filtered, and the water layer was removed, and the organic layer dried over (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 8% ethyl acetate in dichloromethane to provide the desired product. MS (ESI(−)Q1MS) m/z 346 (M−H)−.

Workup

  1. temperaturecooled to 0° C.
  2. stirringstirred for 2 hours at 25° C.
  3. stirringstirred it 65° C. for 15 hours
  4. temperaturecooled
  5. filtrationThe precipitated zinc salts were filtered
  6. customthe water layer was removed
  7. dry with materialthe organic layer dried over (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe concentrate was purified by flash column chromatography on silica gel with 8% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-d5132172fe0b4164922555b46eadfa86
Source dataset
uspto-grants-2003_07
Patent number
US06593480B2

Reaction notes

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