Reaction #3361

Reaction equation

2-[2-(1-carboxy-2-methylbutylcarbamoyl) phenyldisulfanylbenzoylamino]-3-methylpentanoic acid

bromine

→

title compound

3-Methyl-2-(3-oxo-3h-benzo[d]isothiazol-2-yl)pentanoic acid

Solvents

dichloromethane

Conditions

Workup

1. 1
   Concentrationconcentrated to dryness in vacuo
2. 2
   OtherThe residue was triturated with dichloromethane
3. 3
   OtherThe dichloromethane was removed by evaporation in vacuo
4. 4
   Otherto remove excess bromine
5. 5
   OtherThe residue was partitioned between dichloromethane/5% aqueous sodium bicarbonate (200 mL each)
6. 6
   OtherThe aqueous layer was separated
7. 7
   Washwashed with fresh dichloromethane
8. 8
   ExtractionThe acidic aqueous solution was extracted with dichloromethane (2×75 mL)
9. 9
   Washwashed with water
10. 10
    Dryingdried (MgSO4)
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated to dryness in vacuo

Procedure

To a stirred suspension of 5.3 g (10.0 mmol) of [S-(R*,R*)]-2-[2-[2-(1-carboxy-2-methylbutylcarbamoyl) phenyldisulfanylbenzoylamino]-3-methylpentanoic acid (from Preparation 19) in 200 mL of dichloromethane was added dropwise 2.4 g (15.0 mmol) of liquid bromine. The reaction mixture was stirred at room temperature for 2 hours and concentrated to dryness in vacuo. The residue was triturated with dichloromethane. The dichloromethane was removed by evaporation in vacuo to remove excess bromine. The residue was partitioned between dichloromethane/5% aqueous sodium bicarbonate (200 mL each). The aqueous layer was separated, washed with fresh dichloromethane, and acidified to pH 1.5 with 6.0M hydrochloric acid. The acidic aqueous solution was extracted with dichloromethane (2×75 mL). The organic layers were combined, washed with water, dried (MgSO4), filtered and concentrated to dryness in vacuo to give 4.8 g of the title compound, mp 50°-52° C.

Source