Sodium hydride → (E)-ethyl 3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-acetoxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)-2-methylacrylate

HRID 524467Notes

Reaction equation

HRID 524467 reaction equation
C(OP([CH:9]([CH3:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[H-].[Na+].[C:18]([O:21][C@H:22]1[CH2:39][CH2:38][C@@:37]2([CH3:40])[C@@H:24]([CH2:25][CH2:26][C@:27]3([CH3:51])[C@@H:36]2[CH2:35][CH2:34][C@H:33]2[C@@:28]3([CH3:50])[CH2:29][CH2:30][C@@:31]3([CH:48]=O)[CH2:43][C:42](=[O:44])[C:41]([CH:45]([CH3:47])[CH3:46])=[C:32]32)[C:23]1([CH3:53])[CH3:52])(=[O:20])[CH3:19]>CN(C=O)C>[C:18]([O:21][C@H:22]1[CH2:39][CH2:38][C@@:37]2([CH3:40])[C@@H:24]([CH2:25][CH2:26][C@:27]3([CH3:51])[C@@H:36]2[CH2:35][CH2:34][C@H:33]2[C@@:28]3([CH3:50])[CH2:29][CH2:30][C@@:31]3(/[CH:48]=[C:9](\[CH3:15])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:43][C:42](=[O:44])[C:41]([CH:45]([CH3:46])[CH3:47])=[C:32]32)[C:23]1([CH3:52])[CH3:53])(=[O:20])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 107155Triethyl 2-phosphonopropionateHCID 88915627(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-formyl-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate

Product 1

HCID 89661748(E)-ethyl 3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-acetoxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)-2-methylacrylateYield 12.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of ethyl 2-(diethoxyphosphoryl)propanoate (3.12 g, 13.09 mmol) in DMF (35 mL) stirred under nitrogen at 0° C. was added NaH (0.60 g, 80 wt %, 20 mmol) during 5 min and stirred for 10 mins. The solution was warmed to rt and stirred for 30 mins before (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-formyl-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate (5.0 g, 10 mmol) was added to above mixture. After overnight, the reaction was quenched with water and washed with saturated NaHCO3 and water. The solid was solved into EtOAc, dried over Na2SO4, filtered and concentrated to remove the majority of solvent. The residue was recrystallized from petroleum ether/EtOAc (8:1), filtered and the filtrate was concentrated to give the residue, which was purified by silica gel eluting with petroleum ether/EtOAc (15:1-10:1) to obtain the product (E)-ethyl 3-((3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-acetoxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)-2-methylacrylate (1.0 g, 1.291 mmol, 12.82%) as a yellow solid.

Workup

  1. stirringstirred for 10 mins
  2. temperatureThe solution was warmed to rt
  3. additionwas added to above mixture
  4. customthe reaction was quenched with water
  5. washwashed with saturated NaHCO3 and water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto remove the majority of solvent
  10. customThe residue was recrystallized from petroleum ether/EtOAc (8:1)
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated
  13. customto give the residue, which
  14. customwas purified by silica gel eluting with petroleum ether/EtOAc (15:1-10:1)

Sources & evidence

ORD record
ord-2ba0e52a031f447a93489ab6918911ee
Source dataset
uspto-grants-2016_05
Patent number
US09340513B2

Reaction notes

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