Cesium carbonate → Ethyl 5-(3,4-dimethylpiperazin-1-yl)thiophene-2-carboxylate

HRID 1092068ノート

反応式

HRID 1092068 の反応式
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1.[CH3:12][N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH:14]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.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:19][CH:14]1[N:13]([CH3:12])[CH2:18][CH2:17][N:16]([C:2]2[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=2)[CH2:15]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 198037DimethylpiperazineHCID 605723Ethyl 5-bromothiophene-2-carboxylateHCID 634876Binap, (A+-)-

生成物 1

HCID 57440412Ethyl 5-(3,4-dimethylpiperazin-1-yl)thiophene-2-carboxylate収率 47.7%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

Palladium(II) acetate (0.112 g, 0.50 mmol) was added to a mixture of ethyl 5-bromothiophene-2-carboxylate (0.571 g, 5 mmol), 1,2-dimethyl-piperazine (1.175 g, 5 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.311 g, 0.50 mmol) and cesium carbonate (2.281 g, 7.00 mmol) in toluene (50.0 ml) at 20° C. under nitrogen. The resulting suspension was stirred at 110° C. for 23 h. The crude product was purified by ion exchange chromatography, using a SCX2 column. The crude material was dissolved in methanol and then applied to the column. The desired product was eluted from the column using 2M NH3 in methanol and pure fractions were evaporated to dryness to afford the crude product as a brown oil. This material was further purified by silica column chromatography, eluting with a gradient of 1 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 5-(3,4-dimethylpiperazin-1-yl)thiophene-2-carboxylate (0.640 g, 47.7%) as a light brown solid.

後処理

  1. customThe crude product was purified by ion exchange chromatography
  2. dissolutionThe crude material was dissolved in methanol
  3. washThe desired product was eluted from the column
  4. customwere evaporated to dryness
  5. customto afford the crude product as a brown oil
  6. customThis material was further purified by silica column chromatography
  7. washeluting with a gradient of 1 to 5% MeOH in DCM
  8. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-60983b7f5cf940db83db7a6851f5e5a3
出典データセット
uspto-grants-2012_03
特許番号
US08129391B2

反応ノート

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