Sodium Carbonate → Abiraterone Acetate

HRID 1451360Notes

Reaction equation

HRID 1451360 reaction equation
C(B(CC)[C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)C.FC(F)(F)S(O[C:18]1[C@:19]2([CH2:36][CH2:35][C@H:34]3[C@@H:24]([CH2:25][CH:26]=[C:27]4[C@:32]3([CH3:33])[CH2:31][CH2:30][C@H:29]([O:37][C:38](=[O:40])[CH3:39])[CH2:28]4)[C@@H:21]2[CH2:22][CH:23]=1)[CH3:20])(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:38]([O:37][C@H:29]1[CH2:30][CH2:31][C@@:32]2([CH3:33])[C:27](=[CH:26][CH2:25][C@@H:24]3[C@@H:34]2[CH2:35][CH2:36][C@@:19]2([CH3:20])[C@H:21]3[CH2:22][CH:23]=[C:18]2[C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)[CH2:28]1)(=[O:40])[CH3:39]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 6428513-(Diethylboryl)pyridineHCID 10457059((3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(trifluoromethylsulfonyloxy)-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta(a)phenanthren-3-yl) acetate

Product 1

HCID 9821849Abiraterone AcetateYield 84.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Diethyl(3-pyridyl)borane (3.38 g, 23 mmol) from Aldrich Chemical Co. Ltd. was added to a stirred solution of 3β-acetoxyandrosta-5,16-dien-17-yl trifluoromethanesulphonate (6.94 g, 15 mmol) in THF (75 ml) containing bis(triphenylphosphine)palladium(II) chloride (0.105 g, 0.15 mmol). An aqueous solution of sodium carbonate (2M, 30 ml) was then added and the mixture heated, with stirring, by an oil bath at 80° C. for 1 h, and allowed to cool. The mixture was partitioned between diethyl ether and water, the ether phase was dried (Na2CO3), filtered through a short plug of silica, and concentrated. Chromatography, on elution with light petroleum-diethyl ether (2:1), afforded the title compound (4.95 g, 84%) which crystallised from hexane, m.p. 144°-145° C., 1H-NMR(CDCl3) inter alia δ1.05(3H,s, 19-CH3), 1.08(3H,s,18-CH3), 2.04(3H,s,CH3CO2), 4.60(1H,m,3α-H), 5.42(1H,dm, J 4.7 Hz,6-H), 5.99(1H,m,16-H), 7.23(1H,m,Py 5-H) 7.65(1H,m,Py 4-H), 8.46(1H,m,Py 6-H), 8.62(1H,m,Py 2-H). Anal. Calcd: C, 79.75; H, 8.50; N, 3.58. Found: C, 79.78; H, 8.52; N, 3.54%.

Workup

  1. temperaturethe mixture heated
  2. temperatureto cool
  3. customThe mixture was partitioned between diethyl ether and water
  4. dry with materialthe ether phase was dried (Na2CO3)
  5. filtrationfiltered through a short plug of silica
  6. concentrationconcentrated
  7. washChromatography, on elution with light petroleum-diethyl ether (2:1)

Sources & evidence

ORD record
ord-3a0c1ec79a85407285ee08aee84cf153
Source dataset
uspto-grants-1997_02
Patent number
US05604213

Reaction notes

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