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

HRID 85641Notes

Reaction equation

HRID 85641 reaction equation
[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]

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 99644481-Boc-piperidine-3-carboxaldehydeHCID 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)benzoate

Product 1

HCID 68358076tert-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-carboxylateYield 70.9%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 111,2-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

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).

Workup

  1. stirringAfter stirring the mixture for 16.5 h
  2. extractionwas extracted with dichloromethane (3×5 mL)
  3. dry with materialThe combined organic layers were dried with Na2SO4
  4. customThe drying agent was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customwas purified by silica gel flash chromatography
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-253bb6090a464c0fbfe8219890ffe96a
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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