Allyl iodide → 3-((2R,5R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 579177Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 579177
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:23]#[C:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:8][C:9]=1[N:10]1[C:15](=[O:16])[CH2:14][O:13][CH2:12][C@H:11]1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:4].[Li+].[CH3:30][CH:31]([N-]C(C)C)[CH3:32].C(I)C=C>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:23]#[C:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:8][C:9]=1[N:10]1[C@H:11]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:12][O:13][C@H:14]([CH2:32][CH:31]=[CH2:30])[C:15]1=[O:16])=[O:4]

Komponenten

5

Edukt 3

HCID 11166Allyl iodideHCID 2724682Lithium diisopropylamideHCID 666846883-((R)-3-Cyclohexyl-5-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

Produkt 1

HCID 666842053-((2R,5R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl esterAusbeute 9,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 3-((R)-3-Cyclohexyl-5-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (600 mg, 1.49 mmol, 1.0 equiv) in THF (5.0 mL) at −78° C. was added LDA (0.82 mL, 2.0 M in THF, 1.64 mmol, 1.1 equiv) and the resulting solution was stirred at −78° C. for 20 minutes. To the solution was then added allyliodide (300 mg, 1.78 mmol, 1.2 equiv). The solution was warmed to room temperature and stirred at this temperature for 30 minutes. The reaction was quenched by addition of sat. aq. NH4Cl solution. The mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography, EtOAc/heptane 25% to give 3-((2S,5R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl 140 mg, 3-((2R,5R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester 60 mg and mixed fraction 200 mg.

Aufarbeitung

  1. temperatureThe solution was warmed to room temperature
  2. stirringstirred at this temperature for 30 minutes
  3. customThe reaction was quenched by addition of sat. aq. NH4Cl solution
  4. extractionThe mixture was extracted with EtOAc
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography, EtOAc/heptane 25%

Quellen und Nachweise

ORD-Eintrag
ord-1feffb9f819748e0a6ae215e49ca5d2e
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040690B2

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