Morpholine → ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-morpholinoethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate

HRID 1400989Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1400989
[N:1]1([C@:4]23[CH2:40][CH2:39][C@@H:38]([C:41]([CH3:43])=[CH2:42])[C@@H:5]2[C@@H:6]2[C@@:19]([CH3:22])([CH2:20][CH2:21]3)[C@@:18]3([CH3:23])[C@@H:9]([C@:10]4([CH3:37])[C@@H:15]([CH2:16][CH2:17]3)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]3[CH2:31][CH2:30][CH:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:28][CH:27]=3)=[CH:12][CH2:11]4)[CH2:8][CH2:7]2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1>O1CCOCC1>[CH3:22][C@:19]12[C@@:18]3([CH3:23])[C@@H:9]([C@:10]4([CH3:37])[C@@H:15]([CH2:16][CH2:17]3)[C:14]([CH3:24])([CH3:25])[C:13]([C:26]3[CH2:31][CH2:30][CH:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:28][CH:27]=3)=[CH:12][CH2:11]4)[CH2:8][CH2:7][C@@H:6]1[C@H:5]1[C@H:38]([C:41]([CH3:43])=[CH2:42])[CH2:39][CH2:40][C@:4]1([NH:1][CH2:2][CH2:3][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)[CH2:21][CH2:20]2

Komponenten

5

Edukt 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 86692341ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate

Produkt 1

HCID 86692344ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-morpholinoethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylateAusbeute 63,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a flask containing a suspension of ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate (0.202 g, 0.344 mmol) in 1,4-dioxane (3 mL) was added Hunig's base (0.421 mL, 2.408 mmol) followed by morpholine (0.150 mL, 1.720 mmol). The mixture was heated to 100° C. for 15.5 h then was cooled to rt. The mixture was directly purified by flash chromatography using a 0-40% ethyl acetate in hexanes gradient and a 25 g silica gel column. The fractions containing the expected product were combined and were concentrated under reduced pressure to give ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-morpholinoethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate (0.148 g, 0.219 mmol, 63.7% yield) as a white foam. LCMS: m/e 675.8 (M+H)+, 2.06 min (method 1).

Aufarbeitung

  1. additionTo a flask containing
  2. temperaturethen was cooled to rt
  3. customThe mixture was directly purified by flash chromatography
  4. additionThe fractions containing the expected product
  5. concentrationwere concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-465276bd5c234c0bbf511ff7b298e7a4
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906889B2

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