Bromine → 3-Methyl-2-(3-oxobenzo[d]isothiazol-2(3H)-yl)pentanoic acid

HRID 3265Notes

Reaction equation

HRID 3265 reaction equation
C(C(NC([C:12]1[CH:36]=[CH:35][CH:34]=[CH:33][C:13]=1[C:14]([N:16]([S:25]SC1C=CC=CC=1)[CH:17]([CH:21]([CH3:24])[CH2:22][CH3:23])[C:18]([OH:20])=[O:19])=[O:15])=O)C(C)CC)(O)=O.BrBr>ClCCl>[CH3:24][CH:21]([CH2:22][CH3:23])[CH:17]([N:16]1[C:14](=[O:15])[C:13]2[CH:33]=[CH:34][CH:35]=[CH:36][C:12]=2[S:25]1)[C:18]([OH:20])=[O:19]

Participants

4

Reactant 2

HCID 24408BromineHCID 867540052-[2-(1-Carboxy-2-methylbutylcarbamoyl) phenyldisulfanylbenzoylamino]-3-methylpentanoic acid

Product 1

HCID 178926623-Methyl-2-(3-oxobenzo[d]isothiazol-2(3H)-yl)pentanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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.

Workup

  1. concentrationconcentrated to dryness in vacuo
  2. customThe residue was triturated with dichloromethane
  3. customThe dichloromethane was removed by evaporation in vacuo
  4. customto remove excess bromine
  5. customThe residue was partitioned between dichloromethane/5% aqueous sodium bicarbonate (200 mL each)
  6. customThe aqueous layer was separated
  7. washwashed with fresh dichloromethane
  8. extractionThe acidic aqueous solution was extracted with dichloromethane (2×75 mL)
  9. washwashed with water
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-4067666dc2a34bd280d72f658a8ab4f7
Source dataset
uspto-grants-1998_03
Patent number
US05733921

Reaction notes

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