Cesium carbonate → Ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylate

HRID 16845

Reaktionsgleichung

Reaktionsgleichung von HRID 16845
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[CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:12][N:13]1[CH2:19][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][CH2:14]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 2283491-MethylhomopiperazineHCID 605723Ethyl 5-bromothiophene-2-carboxylateHCID 634876Binap, (A+-)-

Produkt 1

HCID 66589793Ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylateAusbeute 12,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Palladium(II)acetate (0.135 g, 0.60 mmol) was added to ethyl 5-bromothiophene-2-carboxylate (1.411 g, 6 mmol), 1-methyl-1,4-diazepane (0.822 g, 7.20 mmol), BINAP (0.374 g, 0.60 mmol) and cesium carbonate (2.74 g, 8.40 mmol) in dioxane (40 mL) warmed to 80° C. for 18 h under nitrogen. The crude reaction mixture was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 7M NH3/MeOH. Fractions were evaporated to dryness to afford the crude product. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 5% 3M ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxylate (0.204 g, 12.67%) as a yellow gum.

Aufarbeitung

  1. customThe crude reaction mixture
  2. customwas purified by ion exchange chromatography
  3. washThe desired product was eluted from the column
  4. customFractions were evaporated to dryness
  5. customto afford the crude product
  6. customThe crude product was purified by silica column chromatography
  7. washeluting with a gradient of 0 to 5% 3M ammonia/MeOH in DCM
  8. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-0491bb1be2c3466bae7581723a930f93
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737149B2

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