Sodium Carbonate → (1R,3aS,5aR,5bR,7aR,11aS,13aR,13bR)-benzyl 9-((E)-3-ethoxy-3-oxoprop-1-enyl)-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]chrysene-3a-carboxylate

HRID 1773034Notes

Reaction equation

HRID 1773034 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[CH:10]([C@:11]4([CH3:31])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14](OS(C(F)(F)F)(=O)=O)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:32]([C:35]([CH3:37])=[CH2:36])[CH2:33][CH2:34][C@:5]1(C(OCC1C=CC=CC=1)=O)[CH2:4][CH2:3]2.CC1(C)C(C)(C)OB(/[CH:56]=[CH:57]/[C:58]([O:60][CH2:61][CH3:62])=[O:59])O1.[C:64](=[O:67])([O-:66])[O-].[Na+].[Na+]>COCCOC.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>[CH2:61]([O:60][C:58](=[O:59])/[CH:57]=[CH:56]/[C:14]1[C:15]([CH3:22])([CH3:21])[C@H:16]2[C@:11]([CH3:31])([CH2:12][CH:13]=1)[CH:10]1[C@:19]([CH3:20])([C@@:2]3([CH3:1])[C@H:7]([CH2:8][CH2:9]1)[C@H:6]1[C@H:32]([C:35]([CH3:37])=[CH2:36])[CH2:33][CH2:34][C@:5]1([C:64]([O:66][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:67])[CH2:4][CH2:3]3)[CH2:18][CH2:17]2)[CH3:62]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 23553751(E)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylateHCID 86666257(1R,3aS,5aR,5bR,7aR,11aR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate

Product 1

HCID 86731492(1R,3aS,5aR,5bR,7aR,11aS,13aR,13bR)-benzyl 9-((E)-3-ethoxy-3-oxoprop-1-enyl)-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]chrysene-3a-carboxylateYield 43%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (1R,3aS,5aR,5bR,7aR,11aR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate, prepared as described in WO2011153315, (50 mg, 0.074 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (66.8 mg, 0.295 mmol), tetrakis(triphenylphosphine)palladium (8.54 mg, 0.0074 mmol) and sodium carbonate (39 mg, 0.369 mmol) in DME (1 mL) and water (1 mL) was heated to 100° C. for 1.5 hours. The reaction mixture was cooled to rt, extracted with ethyl acetate (3×5 mL). The extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography with 80-100% ethyl acetate/hexanes gradient to provide the title compound (20 mg, 43%). LCMS: m/e 627.55 (M+H)+, 3.60 min (method 6).

Workup

  1. customprepared
  2. temperatureThe reaction mixture was cooled to rt
  3. extractionextracted with ethyl acetate (3×5 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by flash chromatography with 80-100% ethyl acetate/hexanes gradient

Sources & evidence

ORD record
ord-73b6bb0e12534913ab3df938ff01fb76
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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