Acetic Acid → HCID 86740640, compound

HRID 1285317Notes

Reaction equation

HRID 1285317 reaction equation
C#C.[CH2:3]([Li])[CH2:4]CC.[CH3:8][C:9]1[C:26]2[C@:21]([CH3:28])([CH2:22][CH2:23][C:24](=[O:27])[CH:25]=2)[C@@H:20]2[C@H:11]([C@H:12]3[C@@:16]([CH2:18][CH2:19]2)([CH3:17])[C:15](=[O:29])[C:14](=[CH2:30])[CH2:13]3)[CH:10]=1.C(O)(=O)C.P([O-])([O-])([O-])=O>C1COCC1.CO.C(OCC)(=O)C>[C:3]([C@:15]1([OH:29])[C:14](=[CH2:30])[CH2:13][C@H:12]2[C@H:11]3[C@H:20]([CH2:19][CH2:18][C@:16]12[CH3:17])[C@:21]1([CH3:28])[C:26](=[CH:25][C:24](=[O:27])[CH2:23][CH2:22]1)[C:9]([CH3:8])=[CH:10]3)#[CH:4]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 1061PhosphateHCID 6326Acetylene3×HCID 54425312HCID 54425312, compoundHCID 178418339Butyllithium

Product 1

HCID 86740640HCID 86740640, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Acetylene saturated THF (45 ml, 4.2 equivalents) was cooled to -72° over 5 min while addition of acetylene continued. The acetylene bubbling was stopped and n-butyl lithium (1.55M, 16.6 ml, 4.0 equivalents) was added over 15 min keeping the temperature less than -65°, mostly at -68°. The mixture was cooled to -90° and added to 6-methyl-16-methyleneandrosta-4,6-diene-3,17-dione. (IIIA, Example 11, 2.0 g) in THF (10 ml) previously cooled to -105° via an insulated teflon canula over about 3 min. The mixture was exothermically warmed to -87° and was recooled to -90° (bath at -93°). After 3.5 hr TLC indicated the reaction was complete. Acetic acid (1.84 ml, 5 equivalents) was added in methanol (10 ml) previously cooled to -98°. The mixture was warmed to 20°-25° and phosphate buffer (20 ml) and ethyl acetate (20 ml) were added. The layers were separated. The organic layer was washed with buffer/saline (1/1). The aqueous layer was back extracted with ethyl acetate which was washed with saline. The organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to an oil. Ethyl acetate was added along with a seed crystal and the mixture sat over night at 20°-25°, and then -20° for 4 hr. The crystals were obtained by filtration, washed with ethyl acetate/hexane: (1/1) to give the title compound.

Workup

  1. customthe temperature less than -65°
  2. custommostly at -68°
  3. temperatureThe mixture was cooled to -90°
  4. temperatureThe mixture was exothermically warmed to -87°
  5. customwas recooled to -90°
  6. custom(bath at -93°)
  7. temperaturepreviously cooled to -98°
  8. temperatureThe mixture was warmed to 20°-25°
  9. customThe layers were separated
  10. washThe organic layer was washed with buffer/saline (1/1)
  11. extractionThe aqueous layer was back extracted with ethyl acetate which
  12. washwas washed with saline
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure to an oil
  16. additionEthyl acetate was added along with a seed crystal
  17. waitthe mixture sat over night at 20°-25°
  18. wait-20° for 4 hr
  19. customThe crystals were obtained by filtration
  20. washwashed with ethyl acetate/hexane

Sources & evidence

ORD record
ord-4261f7e7fa944ae08a4279a8ad56b668
Source dataset
uspto-grants-1986_01
Patent number
US04567001

Reaction notes

Loading…