Bromine → HCID 58432991, compound

HRID 388419Notes

Reaction equation

HRID 388419 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:9]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[N:10][S:11][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[Br:25]Br>C1COCC1>[C:1]([O:5][C:6]([C:8]1[C:9]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)=[N:10][S:11][C:12]=1[Br:25])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24408BromineHCID 584329861,1-Dimethylethyl 3-(4-chlorophenyl)-4-isothiazolecarboxylateHCID 178418339Butyllithium

Product 1

HCID 58432991HCID 58432991, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8 (3.50 g) in THF (60 ml) is cooled to −78° C. under N2 followed by drop wise addition of BuLi (8.0 ml, 1.6M in hexane). After complete addition stirring is continued at −78° C. for 15 min. Bromine (1.2 ml) is now added drop wise and stirring is continued at −78° C. for 15 min, after which the cooling bath is removed. The mixture is allowed to warm to room temp. TLC shows a good conversion into a slightly faster moving spot (Hep/EA, 9/1). 1N HCl (50 ml) is added and the THF is removed in vacuo. Water (100 ml), containing some sodium thiosulfate, is added and the product is extracted with EtOAc (150 ml). The organic layer is washed with sat. NaHCO3, brine, dried and concentrated. The orange/red oily residue is purified by flash column chromatography (˜50 g silica, 5% diisopropyl ether in heptane) yielding 3.1 g of 9 as a pale yellow oil.

Workup

  1. additionAfter complete addition
  2. stirringstirring
  3. waitis continued at −78° C. for 15 min
  4. customafter which the cooling bath is removed
  5. addition1N HCl (50 ml) is added
  6. customthe THF is removed in vacuo
  7. additionWater (100 ml), containing some sodium thiosulfate
  8. additionis added
  9. extractionthe product is extracted with EtOAc (150 ml)
  10. washThe organic layer is washed with sat. NaHCO3, brine
  11. customdried
  12. concentrationconcentrated
  13. customThe orange/red oily residue is purified by flash column chromatography (˜50 g silica, 5% diisopropyl ether in heptane)

Sources & evidence

ORD record
ord-a97795fa1fd740c3969ee2efc93f8305
Source dataset
uspto-grants-2013_02
Patent number
US08377953B2

Reaction notes

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