HCID 86684774, Verbindung → HCID 66685241, Verbindung

HRID 579208Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 579208
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][CH:23]=[O:24])[C:11]1=[O:25])=[O:4].[CH3:32][Mg+].[Br-]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][C@H:23]([OH:24])[CH3:32])[C:11]1=[O:25])=[O:4].[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][C@@H:23]([OH:24])[CH3:32])[C:11]1=[O:25])=[O:4]

Komponenten

5

Edukt 2

HCID 86684774HCID 86684774, VerbindungHCID 178418689HCID 178418689, Verbindung

Produkt 2

HCID 66683972HCID 66683972, VerbindungAusbeute 29 %HCID 66685241HCID 66685241, VerbindungAusbeute 40,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

To a solution of 3-[(2R,5R)-5-cyclohexyl-3-oxo-2-(2-oxo-ethyl)-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (1.9 g, 4.26 mmol, 1.0 equiv) in THF (200 mL) at −10° C., was added MeMgBr (1.85 mL, 3.0 M solution in THF, 5.54 mmol, 1.3 equiv). The resulting solution was stirred at −10° C. for 20 minutes. The reaction was quenched by addition of 3.0 N HCl aqueous solution until pH=1. The volatile solvent was removed under vacuum and the residue was partitioned between EtOAc (100 mL) and brine (5 mL). The separated organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography [Et2O (2% EtOAc)/Heptane, 25% to 50%] to give 3-[(2R,5R)-5-Cyclohexyl-2-((R)-2-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (0.57 g, 29.0%) and 3-[(2R,5R)-5-Cyclohexyl-2-((S)-2-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (0.80 g, 40.7%). MS: 462.4 [M−H+].

Aufarbeitung

  1. customThe reaction was quenched by addition of 3.0 N HCl aqueous solution until pH=1
  2. customThe volatile solvent was removed under vacuum
  3. customthe residue was partitioned between EtOAc (100 mL) and brine (5 mL)
  4. dry with materialThe separated organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography [Et2O (2% EtOAc)/Heptane, 25% to 50%]

Quellen und Nachweise

ORD-Eintrag
ord-ecd8a7672bf740e69cb85edc9e9206a5
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040690B2

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