Sodium hydride → (2R,4S)-2-Ethyl-4-(5-morpholin-4-yl-pyrimidin-2-ylamino)-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butoxycarbonylmethyl ester

HRID 661460Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 661460
[C:1]([O:5][C:6](=[O:9])[CH2:7][OH:8])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[N+](C1C=CC([O:21][C:22]([N:24]2[C:33]3[C:28](=[CH:29][C:30]([C:34]([F:37])([F:36])[F:35])=[CH:31][CH:32]=3)[C@@H:27]([NH:38][C:39]3[N:44]=[CH:43][C:42]([N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[CH:41][N:40]=3)[CH2:26][C@H:25]2[CH2:51][CH3:52])=O)=CC=1)([O-])=O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([CH2:7][O:8][C:22]([N:24]1[C:33]2[C:28](=[CH:29][C:30]([C:34]([F:35])([F:37])[F:36])=[CH:31][CH:32]=2)[C@@H:27]([NH:38][C:39]2[N:44]=[CH:43][C:42]([N:45]3[CH2:46][CH2:47][O:48][CH2:49][CH2:50]3)=[CH:41][N:40]=2)[CH2:26][C@H:25]1[CH2:51][CH3:52])=[O:21])=[O:9])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 11815394Tert-butyl 2-hydroxyacetateHCID 57972814(2R,4S)-2-Ethyl-4-(5-morpholin-4-yl-pyrimidin-2-ylamino)-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid 4-nitrophenyl ester

Produkt 1

HCID 67140956(2R,4S)-2-Ethyl-4-(5-morpholin-4-yl-pyrimidin-2-ylamino)-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butoxycarbonylmethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Hydroxyacetic acid tert-butyl ester (70 mg) and sodium hydride (60%; 21 mg) were added to a solution of the compound obtained in Example 21 (1) above (200 mg) in tetrahydrofuran (3 ml) and the mixture was stirred at 50° C. for an hour. The reaction mixture was cooled to room temperature, a saturated sodium hydrogen carbonate aqueous solution and ethyl acetate were added and the organic layer was separated, washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (NH-silica gel; hexane:ethyl acetate=9:1→3:2) to give the titled compound (183 mg). MS (m/z): 566 [M+H]+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe organic layer was separated
  3. washwashed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (NH-silica gel; hexane:ethyl acetate=9:1→3:2)

Quellen und Nachweise

ORD-Eintrag
ord-c63c155a5a75443b8ba5e01f3659304e
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084611B2

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