Cesium carbonate → Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)thiophene-2-carboxylate

HRID 43941

Reaktionsgleichung

Reaktionsgleichung von HRID 43941
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10]C)=[O:8])=[CH:4][CH:3]=1.[CH3:12][O:13][C@H:14]1[C@@H:19]([NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:18][CH2:17][NH:16][CH2:15]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+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:23]([O:22][C:21]([NH:20][C@H:19]1[CH2:18][CH2:17][N:16]([C:2]2[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][CH:3]=2)[CH2:15][C@H:14]1[O:13][CH3:12])=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 605723Ethyl 5-bromothiophene-2-carboxylateHCID 634876Binap, (A+-)-HCID 86648490Benzyl cis(+/-)-[3-methoxypiperidin-4-yl]carbamate

Produkt 1

HCID 86648823Methyl cis(+/-)-5-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)thiophene-2-carboxylateAusbeute 60,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A suspension of ethyl 5-bromothiophene-2-carboxylate obtained in Example (244a) (100 mg, 0.45 mmol), benzyl cis(±)-(3-methoxypiperidin-4-yl)-carbamate obtained in Example (40b) (143 mg, 0.54 mmol), palladium acetate (10 mg, 0.05 mmol), BINAP (28 mg, 0.05 mmol) and cesium carbonate (206 mg, 0.63 mmol) in toluene was stirred at 110° C. for 39 hours. The reaction solution was diluted with ethyl acetate, washed with water and brine, and then dried over anhydrous magnesium sulfate. Following filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1) to obtain 110 mg of the title compound as a yellow oily substance (60%).

Aufarbeitung

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1)

Quellen und Nachweise

ORD-Eintrag
ord-bf2627a8c0c149f688c086ae44623de2
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536197B2

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