Reaktion #45121

Reaktionsgleichung

ethyl 5-bromothiophene-2-carboxylate

1-ethylpiperazine

(rac)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

sodium tert-butoxide

→

ethyl 5-(4-ethylpiperazin-1-yl)thiophene-2-carboxylate

Ausbeute 32.0%

Lösungsmittel

methanol

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cooled reaction mixture
2. 2
   Sonstigepurified by ion exchange chromatography
3. 3
   WaschenThe desired product was eluted from the column
4. 4
   Sonstigeevaporated to dryness
5. 5
   Sonstigeto afford crude product
6. 6
   SonstigeThe residue was purified by silica column chromatography
7. 7
   Wascheneluting with a gradient of 0 to 3% 7M NH3/MeOH in DCM
8. 8
   workup.ADDITIONFractions containing desired product
9. 9
   Sonstigewere evaporated to dryness
10. 10
    Sonstigeto give impure orange oil
11. 11
    SonstigeThe impure material was further purified by preparative HPLC
12. 12
    workup.ADDITIONFractions containing the desired compound
13. 13
    Sonstigewere evaporated to dryness

Vorschrift

Tris(dibenzylideneacetone)dipalladium(0) (183 m,g, 0.20 mmol) followed by sodium tert-butoxide (538 mg, 5.60 mmol) was added to ethyl 5-bromothiophene-2-carboxylate (1.034 g, 4.40 mmol), 1-ethylpiperazine (0.51 ml, 4.00 mmol) and (rac)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (249 mg, 0.40 mmol) in toluene (20.00 ml) at 25° C. under nitrogen. The resulting suspension was stirred at 110° C. for 18 h. The cooled reaction mixture was diluted with methanol and purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and evaporated to dryness to afford crude product. The residue was purified by silica column chromatography, eluting with a gradient of 0 to 3% 7M NH3/MeOH in DCM. Fractions containing desired product were evaporated to dryness to give impure orange oil. The impure material was further purified by preparative HPLC, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford ethyl 5-(4-ethylpiperazin-1-yl)thiophene-2-carboxylate (339 mg, 32%) as a yellow oil.

Quelle