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

HRID 16843

反応式

HRID 16843 の反応式
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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e7a71be384af4185896102fb5bbd9536
出典データセット
uspto-grants-2010_06
特許番号
US07737149B2

関連ノート

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