Ammonium Chloride → 1-[2-[(4S)-4-(tert-butyldimethyl-silyloxy)-1,2,3,4-tetrahydroquinolin-1-yl]-4-pyridyl]-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene

HRID 407119Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 407119
Br[C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=3)[CH:11]=[C:10]([C:22]([O:24][CH3:25])=[O:23])[C:9]=2[C:26]([O:28][CH3:29])=[O:27])[CH:5]=[CH:4][N:3]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[Si:48]([O:55][C@@H:56]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[NH:59][CH2:58][CH2:57]1)([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49].CC(C)([O-])C.[Na+].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[Si:48]([O:55][C@@H:56]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[N:59]([C:2]2[CH:7]=[C:6]([C:8]3[C:17]4[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=4)[CH:11]=[C:10]([C:22]([O:24][CH3:25])=[O:23])[C:9]=3[C:26]([O:28][CH3:29])=[O:27])[CH:5]=[CH:4][N:3]=2)[CH2:58][CH2:57]1)([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49]

Komponenten

10

Edukt 5

HCID 25517Ammonium ChlorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 220073291-(2-Bromo-4-pyridyl)-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthaleneHCID 23676156Sodium t-butoxideHCID 66866618(4S)-4-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydroquinoline

Produkt 1

HCID 668676711-[2-[(4S)-4-(tert-butyldimethyl-silyloxy)-1,2,3,4-tetrahydroquinolin-1-yl]-4-pyridyl]-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthaleneAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 20.00 g of 1-(2-bromo-4-pyridyl)-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene in 200 mL of toluene was sonicated under reduced pressure, and then to the solution were added 975 mg of palladium acetate, 1009 mg of tri-tert-butylphosphonium tetrafluoroborate, 13.72 g of (4S)-4-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydroquinoline and 6.26 g of sodium tert-butoxide at room temperature. After nitrogen substitution, the mixture was stirred at 100° C. for 4 hours. After radiation, to the reaction solution were added 100 mL of saturated aqueous ammonium chloride solution, 100 mL of water and 100 mL of ethyl acetate, and the mixture was filtered through Celite®. Celite® was washed with 100 mL of ethyl acetate, and then the organic layer was separated. The organic layer was washed with 100 g of 20% saline, dried over magnesium sulfate, and then concentrated. The resulting residue was purified by column chromatography on silica gel (n-hexan/ethyl acetate=5/1 to 4/1) to give 22.31 g of 1-[2-[(4S)-4-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydroquinolin-1-yl]-4-pyridyl]-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene (yield: 80%).

Aufarbeitung

  1. filtrationthe mixture was filtered through Celite®
  2. washCelite® was washed with 100 mL of ethyl acetate
  3. customthe organic layer was separated
  4. washThe organic layer was washed with 100 g of 20% saline
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by column chromatography on silica gel (n-hexan/ethyl acetate=5/1 to 4/1)

Quellen und Nachweise

ORD-Eintrag
ord-9eeaa7a1c1fc4f50bff5b555ad949f3c
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754221B2

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