Phosphoric Acid → ethyl 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)cyclohex-3-enecarboxylate

HRID 1400985Notes

Reaction equation

HRID 1400985 reaction equation
FC(F)(F)S(O[C:7]1[C:8]([CH3:36])([CH3:35])[C@H:9]2[C@:22]([CH3:25])([CH2:23][CH:24]=1)[C@@H:21]1[C@:12]([CH3:34])([C@@:13]3([CH3:33])[C@H:18]([CH2:19][CH2:20]1)[C@H:17]1[C@H:26]([C:29]([CH3:31])=[CH2:30])[CH2:27][CH2:28][C@:16]1([NH2:32])[CH2:15][CH2:14]3)[CH2:11][CH2:10]2)(=O)=O.P(=O)(O)(O)O.[K].CC1(C)C(C)(C)OB([C:53]2[CH2:58][CH2:57][CH:56]([C:59]([O:61][CH2:62][CH3:63])=[O:60])[CH2:55][CH:54]=2)O1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:32][C@:16]12[CH2:28][CH2:27][C@@H:26]([C:29]([CH3:31])=[CH2:30])[C@@H:17]1[C@@H:18]1[C@@:13]([CH3:33])([CH2:14][CH2:15]2)[C@@:12]2([CH3:34])[C@@H:21]([C@:22]3([CH3:25])[C@@H:9]([CH2:10][CH2:11]2)[C:8]([CH3:35])([CH3:36])[C:7]([C:53]2[CH2:58][CH2:57][CH:56]([C:59]([O:61][CH2:62][CH3:63])=[O:60])[CH2:55][CH:54]=2)=[CH:24][CH2:23]3)[CH2:20][CH2:19]1

Participants

9

Reactant 5

HCID 1004Phosphoric AcidHCID 5462222PotassiumHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 592787964-(4,4,5,5-Tetramethyl-(1,3,2)dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylic acid ethyl esterHCID 71698571(1R,3aS,5aR,5bR,7aR,11aR,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 trifluoromethanesulfonate

Product 1

HCID 86692333ethyl 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)cyclohex-3-enecarboxylateYield 65.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a flask containing (1R,3aS,5aR,5bR,7aR,11aR,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 trifluoromethanesulfonate (1.22 g, 2.187 mmol) was added phosphoric acid, potassium salt (1.393 g, 6.56 mmol), ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (0.613 g, 2.187 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-phos) (0.067 g, 0.164 mmol), and palladium(II)acetate (0.025 g, 0.109 mmol). The mixture was diluted with 1,4-dioxane (10 mL) and water (1 mL), was flushed with nitrogen, then was sealed and heated to 75° C. After 15 h of heating, the mixture was cooled to rt and was concentrated under reduced pressure. The residue was diluted with water (40 mL) and was extracted with ethyl acetate (3×50 mL). The organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography using a 10-70% EtOAc in hexanes gradient and an 80 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give ethyl 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)cyclohex-3-enecarboxylate (806 mg, 1.434 mmol, 65.6% yield) as an off-white solid. LCMS: m/e 562.7 (M+H)+, 2.17 min (method 1).

Workup

  1. customwas flushed with nitrogen
  2. customwas sealed
  3. temperatureAfter 15 h of heating
  4. temperaturethe mixture was cooled to rt
  5. concentrationwas concentrated under reduced pressure
  6. additionThe residue was diluted with water (40 mL)
  7. extractionwas extracted with ethyl acetate (3×50 mL)
  8. washThe organic layers were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash chromatography
  13. additionThe fractions containing the expected product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f7f87cceb6a5470eb49f06ab11acd7ce
Source dataset
uspto-grants-2014_12
Patent number
US08906889B2

Reaction notes

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