Benzyl Bromide → 3-Benzyl 1-methyl 4-hydroxyisophthalate

HRID 529007Notes

Reaction equation

HRID 529007 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C.O>[OH:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][C:3]=1[C:4]([O:6][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:5]

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 127170602-Hydroxy-5-(methoxycarbonyl)benzoic acid

Product 1

HCID 710610173-Benzyl 1-methyl 4-hydroxyisophthalateYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-hydroxy-5-(methoxycarbonyl)benzoic acid (4.0 g, 20.4 mmol) in DMF (40 mL) was added KHCO3 (2.04 g, 20.4 mmol) and benzyl bromide (3.49 g, 20.4 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and stirring was continued for 20 h. The reaction mixture was diluted with water, extracted with EtOAc (2×) and the combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. The crude material was purified by flash chromatography (gradient from 0% to 30% EtOAc/hexanes) to provide the title compound (5.3 g, 92%) as an off-white solid. 1H NMR (CDCl3) δ 11.21 (s, 1H), 8.58 (d, J=2.0 Hz, 1H), 8.11 (dd, J=8.8, 2.4 Hz, 1H), 7.47-7.37 (m, 5H), 7.01 (d, J=8.8 Hz, 1H), 5.42 (s, 2H), 3.89 (s, 3H); MS(ESI−) m/z 285.2 (M−H)−.

Workup

  1. extractionextracted with EtOAc (2×)
  2. washthe combined organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a crude oil
  7. customThe crude material was purified by flash chromatography (gradient from 0% to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-78bfc3009fe34efa8203bea23735bd52
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

Loading…