Sodium Carbonate Monohydrate → methyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-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)spiro[3.3]hept-5-ene-2-carboxylate

HRID 1400974

Reaktionsgleichung

Reaktionsgleichung von HRID 1400974
FC(F)(F)S(O[C:7]1[C:8]([CH3:36])([CH3:35])[C@H:9]2[C@:22]([CH3:25])([CH2:23][CH:24]=1)[C@@H:21]1[C@:12]([CH3:34])([C@@:13]3([CH3:33])[C@H:18]([CH2:19][CH2:20]1)[C@H:17]1[C@H:26]([C:29]([CH3:31])=[CH2:30])[CH2:27][CH2:28][C@:16]1([NH2:32])[CH2:15][CH2:14]3)[CH2:11][CH2:10]2)(=O)=O.CC1(C)C(C)(C)OB([C:47]2[CH2:57][C:49]3([CH2:52][CH:51]([C:53]([O:55][CH3:56])=[O:54])[CH2:50]3)[CH:48]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:32][C@:16]12[CH2:28][CH2:27][C@@H:26]([C:29]([CH3:31])=[CH2:30])[C@@H:17]1[C@@H:18]1[C@@:13]([CH3:33])([CH2:14][CH2:15]2)[C@@:12]2([CH3:34])[C@@H:21]([C@:22]3([CH3:25])[C@@H:9]([CH2:10][CH2:11]2)[C:8]([CH3:35])([CH3:36])[C:7]([C:47]2[CH2:57][C:49]4([CH2:50][CH:51]([C:53]([O:55][CH3:56])=[O:54])[CH2:52]4)[CH:48]=2)=[CH:24][CH2:23]3)[CH2:20][CH2:19]1

Komponenten

7

Edukt 3

HCID 2735133Sodium Carbonate MonohydrateHCID 71698571(1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-amino-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 trifluoromethanesulfonateHCID 86692319Methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[3.3]hept-5-ene-2-carboxylate

Produkt 1

HCID 86692318methyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-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)spiro[3.3]hept-5-ene-2-carboxylateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a vial containing (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-amino-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 trifluoromethanesulfonate (0.418 g, 0.749 mmol) was added methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[3.3]hept-5-ene-2-carboxylate (0.250 g, 0.899 mmol), sodium carbonate monohydrate (0.232 g, 1.874 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.026 g, 0.022 mmol). The mixture was diluted with 1,4-dioxane (4 mL) and water (1 mL), then was flushed with nitrogen and the vial was sealed and heated to 85° C. After 5.5 h of heating, the mixture was cooled to rt, concentrated under reduced pressure, adsorbed to silica gel, and purified by chromatography using a 0-45% ethyl acetate in hexanes gradient and a 40 g Thomson silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-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)spiro[3.3]hept-5-ene-2-carboxylate (0.31 g, 0.554 mmol, 73.9% yield) as an off-white solid. 1H NMR showed a mixture of the two diastereomers (0.8:1 ratio) which were not separated and were used in the next step with no additional purification. LCMS: m/e 560.47 (M+H)+, 2.46 min (method 2). Mixture of diastereomers: 1H NMR (500 MHz, chloroform-d) δ=6.00 (s, 0.45H, minor diastereomer), 5.84 (s, 0.55H, major diastereomer), 5.54 (td, J=6.1, 2.2 Hz, 1H), 4.75 (d, J=2.0 Hz, 1H), 4.62 (dd, J=2.3, 1.3 Hz, 1H), 3.71 (m, 3H), 3.13-2.99 (m, 1H), 2.70-2.31 (m, 7H), 2.18-1.84 (m, 4H), 1.72 (s, 3H), 1.18 (d, J=3.5 Hz, 3H), 1.10-1.08 (m, 6H), 0.99 (s, 3H), 0.85 (s, 3H), 1.68-0.83 (m, 19H).

Aufarbeitung

  1. customwas flushed with nitrogen
  2. customthe vial was sealed
  3. temperatureAfter 5.5 h of heating
  4. temperaturethe mixture was cooled to rt
  5. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-b94ea3e7da534b70954c05c34a04ea44
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906889B2

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