Sodium triacetoxyborohydride → tert-butyl 3-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-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-3a-ylamino)methyl)piperidine-1-carboxylate
Reaktionsgleichung
[NH2:1][C@:2]12[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:34])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.[C:41]([O:45][C:46]([N:48]1[CH2:53][CH2:52][CH2:51][CH:50]([CH:54]=O)[CH2:49]1)=[O:47])([CH3:44])([CH3:43])[CH3:42].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C([O-])(O)=O.[Na+].CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:31][O:30][C:28]([C:27]1[CH:26]=[CH:25][C:24]([C:11]2[C:12]([CH3:22])([CH3:23])[C@H:13]3[C@:8]([CH3:34])([CH2:9][CH:10]=2)[C@@H:7]2[C@:16]([CH3:21])([C@@:17]4([CH3:20])[C@H:4]([CH2:5][CH2:6]2)[C@H:3]2[C@H:35]([C:38]([CH3:40])=[CH2:39])[CH2:36][CH2:37][C@:2]2([NH:1][CH2:54][CH:50]2[CH2:51][CH2:52][CH2:53][N:48]([C:46]([O:45][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:47])[CH2:49]2)[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:33][CH:32]=1)=[O:29]Komponenten
Edukt 3
HCID 5049666Sodium triacetoxyborohydride
HCID 99644481-Boc-piperidine-3-carboxaldehyde
HCID 68357865methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-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)benzoateProdukt 1
Reagenzien, Katalysatoren, Lösungsmittel 3
Versuchsvorschrift
To a solution of methyl 4-((1R,3aS,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)benzoate (30 mg, 0.055 mmol) in DCE (0.5 mL) was added 3-formyl-piperidine-1-carboxylic acid tert-butyl ester (14.71 mg, 0.069 mmol) and titanium(IV) isopropoxide (0.020 mL, 0.069 mmol). The mixture was stirred at rt for 1 h and sodium triacetoxyborohydride (23.38 mg, 0.110 mmol) was added. After stirring the mixture for 16.5 h, the mixture was diluted with 3 mL of sat. NaHCO3 and was extracted with dichloromethane (3×5 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was adsorbed to silica gel and was purified by silica gel flash chromatography using a 0-10% EtOAc in hexanes gradient and a Thomson 12 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to afford the title compound (29 mg, 0.039 mmol, 70.9% yield) as an off-white film. The product was used in the next step with no additional purification. LCMS: m/e 741.7 (M+H)+, 3.76 min (method 2).
Aufarbeitung
- stirringAfter stirring the mixture for 16.5 h
- extractionwas extracted with dichloromethane (3×5 mL)
- dry with materialThe combined organic layers were dried with Na2SO4
- customThe drying agent was removed by filtration
- concentrationthe filtrate was concentrated under reduced pressure
- customwas purified by silica gel flash chromatography
- additionThe fractions containing the expected product
- concentrationconcentrated under reduced pressure
Quellen und Nachweise
- ORD-Eintrag
- ord-253bb6090a464c0fbfe8219890ffe96a
- Quelldatensatz
- uspto-grants-2014_09
- Patentnummer
- US08846647B2
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