Benzyl Bromide → Methyl 3-(benzyloxy)-4-nitrobenzoate

HRID 1814354Notes

Reaction equation

HRID 1814354 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CC(C)=O>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:9]=[CH:10][C:11]([N+:12]([O-:14])=[O:13])=[C:2]([O:1][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 294866Methyl 3-hydroxy-4-nitrobenzoate

Product 1

HCID 15054012Methyl 3-(benzyloxy)-4-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

REFERENCE: J. Med Chem. 1997, 40, 105-111. To an acetone solution (500 mL) of methyl 3-hydroxy-4-nitrobenzoate (25.0 g, 126.8 mmol) was added cesium carbonate (61.9 g, 190.2 mmol) followed by benzyl bromide (15.0 mL, 126.8 mmol). The reaction was heated to reflux and monitored by TLC. The reaction was judged complete in approximately 7 h. The reaction was then cooled to room temperature and concentrated under reduced pressure to approximately 20 mL. The residue was diluted with ethyl acetate (700 mL) and washed in succession with 1N hydrochloric acid, 1N sodium hydroxide, 1N hydrochloric acid and finally with saturated aqueous sodium chloride. The organic layer was then dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 3-benzyloxy-4-nitro-benzoic acid methyl ester as a solid. 1H NMR (CDCl3) 7.83(m,2H), 7.70(dd, 1H), 7.50-7.30(m,5H), 5.28(s,2H), 3.96(s,3H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux
  3. concentrationconcentrated under reduced pressure to approximately 20 mL
  4. additionThe residue was diluted with ethyl acetate (700 mL)
  5. washwashed in succession with 1N hydrochloric acid, 1N sodium hydroxide, 1N hydrochloric acid and finally with saturated aqueous sodium chloride
  6. dry with materialThe organic layer was then dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dc0473f71127400e9ea9dbe13c87eeda
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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