Cyclopropanecarboxaldehyde → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(cyclopropylmethylamino)-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

HRID 85639Notes

Reaction equation

HRID 85639 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.[CH:41]1([CH:44]=O)[CH2:43][CH2:42]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:41]1([CH2:44][NH:1][C@:2]23[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]2[C@@H:4]2[C@@:17]([CH3:20])([CH2:18][CH2:19]3)[C@@:16]3([CH3:21])[C@@H:7]([C@:8]4([CH3:34])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:22])([CH3:23])[C:11]([C:24]3[CH:25]=[CH:26][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=3)=[CH:10][CH2:9]4)[CH2:6][CH2:5]2)[CH2:43][CH2:42]1

Participants

7

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 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 68358124methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(cyclopropylmethylamino)-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)benzoateYield 100%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

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 (0.022 g, 0.040 mmol) in DCE (0.25 mL) was added cyclopropanecarbaldehyde (2.84 mg, 0.040 mmol) and titanium (IV) isopropoxide (0.015 mL, 0.051 mmol). The mixture was stirred at rt for 1 h and sodium triacetoxyborohydride (0.017 g, 0.081 mmol) was added. After stirring the mixture for 16.75 h, the mixture was diluted with 3 mL of water and was filtered through a pad of celite, then was extracted with dichloromethane (3×4 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give the title compound (0.024 g, 0.040 mmol, 99% yield) as a clear film. The crude product was used in the next step with no additional purification. LCMS: m/e 598.6 (M+H)+, 2.13 min (method 2).

Workup

  1. stirringAfter stirring the mixture for 16.75 h
  2. filtrationwas filtered through a pad of celite
  3. extractionwas extracted with dichloromethane (3×4 mL)
  4. dry with materialThe combined organic layers were dried with Na2SO4
  5. customThe drying agent was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-dd7e8fa498ac4f8ba26f5b5d03e7ac83
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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