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

HRID 1092068노트

반응식

HRID 1092068 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
110 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-60983b7f5cf940db83db7a6851f5e5a3
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129391B2

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