1-Ethylpiperazine → Ethyl 5-(4-ethylpiperazin-1-yl)thiophene-2-carboxylate

HRID 16843

Reaktionsgleichung

Reaktionsgleichung von HRID 16843
CC(C)([O-])C.[Na+].Br[C:8]1[S:12][C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][CH:9]=1.[CH2:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:18]([N:20]1[CH2:25][CH2:24][N:23]([C:8]2[S:12][C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][CH:9]=2)[CH2:22][CH2:21]1)[CH3:19]

Komponenten

8

Edukt 4

HCID 791961-EthylpiperazineHCID 605723Ethyl 5-bromothiophene-2-carboxylateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Produkt 1

HCID 66589785Ethyl 5-(4-ethylpiperazin-1-yl)thiophene-2-carboxylateAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 887MethanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

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.

Aufarbeitung

  1. customThe cooled reaction mixture
  2. custompurified by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. customevaporated to dryness
  5. customto afford crude product
  6. customThe residue was purified by silica column chromatography
  7. washeluting with a gradient of 0 to 3% 7M NH3/MeOH in DCM
  8. additionFractions containing desired product
  9. customwere evaporated to dryness
  10. customto give impure orange oil
  11. customThe impure material was further purified by preparative HPLC
  12. additionFractions containing the desired compound
  13. customwere evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-e7a71be384af4185896102fb5bbd9536
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737149B2

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