Sulfamic Acid → 2-Bromo-5-hydroxy-4-methoxybenzoic acid

HRID 1015919Notes

Reaction equation

HRID 1015919 reaction equation
[Br:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([OH:12])=[CH:6][C:3]=1[CH:4]=[O:5].S(=O)(=O)([OH:15])N.CCOC(C)=O.[Cl:24]([O-:26])=[O:25].[Na+:27]>O>[Cl:24]([O-:26])=[O:25].[Na+:27].[Br:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([OH:12])=[CH:6][C:3]=1[C:4]([OH:15])=[O:5]

Participants

7

Reactant 4

HCID 5987Sulfamic AcidHCID 8857Ethyl AcetateHCID 6160682-Bromo-5-hydroxy-4-methoxybenzaldehyde2×HCID 23668197Sodium Chlorite3×

Product 2

HCID 23668197Sodium ChloriteHCID 441396422-Bromo-5-hydroxy-4-methoxybenzoic acidYield 89%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
5 °C

Procedure

1 Kg of 2-bromo-5-hydroxy-4-methoxy benzaldehyde (B2) and 1.255 Kg of sulfamic acid were added with stirring into a mixture of 4.473 Kg of EtOAc and 8 L of water. The reaction mixture was stirred until all of the solid had dissolved. The reaction mixture was cooled to between −10 and 0° C. An aqueous solution of sodium chlorite was prepared by dissolving 505 g of sodium chlorite in 3 L of water. The sodium chlorite solution was added to the pre-cooled B2 solution at a rate that maintained the reaction temperature under 5° C. After the complete addition of sodium chlorite solution, the reaction mixture was stirred for another hour at 0° C. and was then allowed to warm up to room temperature. The reaction was monitored by TLC. After the TLC analysis showed completion of the reaction, the aqueous layer was separated. The aqueous layer was extracted with EtOAc (1.789 Kg) and the combined organic layer was transferred to another flask and EtOAc was removed by vacuum distillation at 40° C. 6.92 Kg of toluene was added at between 30 to 40° C., the slurry was cooled to between −10 to 0° C. and the precipitate was collected by filtration to give about 950 g (89% (yield) of 2-bromo-5-hydroxy-4-methoxy benzoic acid (B13). 1H NMR (CDCl3) δ 3.95 (3H, s, CH3), 7.22 (1H, s, CH), 7.46 (1H, s, CH).

Workup

  1. dissolutionhad dissolved
  2. temperatureThe reaction mixture was cooled to between −10 and 0° C
  3. stirringthe reaction mixture was stirred for another hour at 0° C.
  4. temperatureto warm up to room temperature
  5. customcompletion of the reaction
  6. customthe aqueous layer was separated
  7. extractionThe aqueous layer was extracted with EtOAc (1.789 Kg)
  8. customthe combined organic layer was transferred to another flask
  9. customEtOAc was removed by vacuum distillation at 40° C
  10. addition6.92 Kg of toluene was added at between 30 to 40° C.
  11. temperaturethe slurry was cooled to between −10 to 0° C.
  12. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-a9aa18fe670c4e56ac688d5c6488c30e
Source dataset
uspto-grants-2011_07
Patent number
US07985879B2

Reaction notes

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