반응 #45121

반응 방정식

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

수율 32.0%

용매

methanol

toluene

반응 조건

후처리

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

실험 절차

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.

출처