Estrone → HCID 12134978, compound

HRID 1750891Notes

Reaction equation

HRID 1750891 reaction equation
[CH3:1][C@@:2]12[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[C@H:14]1[C@@H:5]([C:6]3[CH:7]=[CH:8][C:9]([OH:20])=[CH:10][C:11]=3[CH2:12][CH2:13]1)[CH2:4][CH2:3]2.[C:21]12(O)[CH2:30][CH:25]3[CH2:26][CH:27]([CH2:29][CH:23]([CH2:24]3)[CH2:22]1)[CH2:28]2.B(F)(F)F.CCOCC>CCCCC>[C:21]12([C:8]3[C:9]([OH:20])=[CH:10][C:11]4[CH2:12][CH2:13][C@@H:14]5[C@@H:5]([C:6]=4[CH:7]=3)[CH2:4][CH2:3][C@@:2]3([CH3:1])[C@H:15]5[CH2:16][CH2:17][C:18]3=[O:19])[CH2:30][CH:25]3[CH2:26][CH:27]([CH2:29][CH:23]([CH2:24]3)[CH2:22]1)[CH2:28]2

Participants

5

Reactant 3

HCID 5870Estrone2×HCID 8000Boron trifluoride etherateHCID 641521-Adamantanol

Product 1

HCID 12134978HCID 12134978, compoundYield 76.7%

Reagents, catalysts & solvents 1

HCID 8003PentaneSolvent

Procedure

Estrone [3-hydroxyestra-1,3,5(10)-trien-17-one, 270 mg, 1 mmol) and 1-adamantanol (170 mg, 1 mmol) were added to anhydrous n-pentane (6 mL) and the stirred mixture was cooled with an ice bath. Boron trifluoride etherate (BF3.EtOEt, 0.4 mL) was added over a 10 minute period. After an additional 15 minutes, the ice bath was removed and stirring was continued for an additional 45 minutes at room temperature. During the 45 minute period, solids present in the reaction mixture were dissolved and a yellow oil formed. Crushed ice was then added while shaking and swirling the reaction flask and a pink solid was formed. The filtered, crude pink product was washed with water until the filtrate had a neutral pH, and then the solid was dried in a vacuum oven at 50° C. The crude pink powder (0.4 g) was purified by flash chromatography (silica gel eluted with 20% ethyl acetate in hexanes) to get the pure product (0.31 g, 76.7%). The product was recrystallized from a mixture of chloroform and isopropyl alcohol and characterized as follows: (i) melting point=322-324° C. (see, e.g., Lunn, W. H. W.; Farkas, E., Adamantyl Carbonium Ion as a Dehydrogenating Agent: Its Reactions with Estrone, Tetrahedron 1969, 24, 6773-76, citing melting point as 295-296° C.); (ii) 1H NMR (CDCl3, 300 MHZ) δ0.94 (s, 3H, C18—CH3), 2.8 (m, 2H, C6CH2), 4.7 (s, 1H, C3—OH), 6.4 (5, 1H, C4—H), 7.12 (5, 1H, C1—H); (iii) 13C NMR CDCl3, 300 MHZ) δ3.76, 21.47, 25.93, 26.41, 28.63, 28.95 (3×C), 31.56, 35.81, 36.56, 36.98 (3×C), 38.42, 40.69 (3×C), 44.25, 47.99, 50.35, 116.87, 124.11, 131.59, 134.00, 135.02, 152.44, 221.43. (Chemical Abstracts Registry Number [21003-01-0].)

Workup

  1. temperaturethe stirred mixture was cooled with an ice bath
  2. customthe ice bath was removed
  3. waitwas continued for an additional 45 minutes at room temperature
  4. dissolutionDuring the 45 minute period, solids present in the reaction mixture were dissolved
  5. customa yellow oil formed
  6. additionCrushed ice was then added
  7. stirringwhile shaking
  8. customa pink solid was formed
  9. washThe filtered, crude pink product was washed with water until the filtrate
  10. customthe solid was dried in a vacuum oven at 50° C
  11. customThe crude pink powder (0.4 g) was purified by flash chromatography (silica gel eluted with 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c05572344fe64c8bbe76b1a25fa7f3a2
Source dataset
uspto-grants-2015_10
Patent number
US09156876B2

Reaction notes

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