Reaktion #475601

Reaktionsgleichung

8

3-(4-Chloro-phenyl)-isothiazole-4-carboxylic acid tert-butyl ester

BuLi

Bromine

→

9

5-Bromo-3-(4-chloro-phenyl)-isothiazole-4-carboxylic acid tert-butyl ester

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter complete addition
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITis continued at −78° C. for 15 min
4. 4
   Sonstigeafter which the cooling bath is removed
5. 5
   workup.ADDITION1N HCl (50 ml) is added
6. 6
   Sonstigethe THF is removed in vacuo
7. 7
   workup.ADDITIONWater (100 ml), containing some sodium thiosulfate
8. 8
   workup.ADDITIONis added
9. 9
   Extraktionthe product is extracted with EtOAc (150 ml)
10. 10
    WaschenThe organic layer is washed with sat. NaHCO3, brine
11. 11
    Sonstigedried
12. 12
    Einengenconcentrated
13. 13
    SonstigeThe orange/red oily residue is purified by flash column chromatography (˜50 g silica, 5% diisopropyl ether in heptane)

Vorschrift

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.

Quelle