Hydrochloric Acid → Gestodene

HRID 1472961Notes

Reaction equation

HRID 1472961 reaction equation
[C:1]([Mg]Br)#[CH:2].[CH2:5]1COC[CH2:6]1.C([O:12][C:13]1[CH2:31][CH2:30][C@H:29]2[C:15](=[CH:16][CH2:17][C@@H:18]3[C@@H:28]2[CH2:27]C[C@@:23]2([CH2:24]C)[C@H:19]3[CH:20]=[CH:21][C:22]2=[O:32])[CH:14]=1)C.Cl>CC1OCCC1.CCO>[C:23]([C@:22]1([OH:32])[CH:21]=[CH:20][C@H:19]2[C@H:18]3[C@H:28]([CH2:27][CH2:1][C@:2]12[CH2:5][CH3:6])[C@@H:29]1[C:15](=[CH:14][C:13](=[O:12])[CH2:31][CH2:30]1)[CH2:16][CH2:17]3)#[CH:24]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 67364108HCID 67364108, compoundHCID 178418486HCID 178418486, compound

Product 1

HCID 3033968GestodeneYield 75%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 73012-MethyltetrahydrofuranSolvent

Procedure

A 0.5 M solution of ethynylmagnesium bromide in THF (200 ml, 100 mmol) was added under a nitrogen atmosphere to a solution of 3-ethoxy-18-methyl-estra-3,5,15-trien-17-one (20 g, 64.1 mmol) in 2-MeTHF (40 ml) without exceeding 25° C. The mixture was stirred at room temperature for 2 h, cooled to 7° C. and EtOH (10 ml) was added. The mixture was stirred for 10 min, 3N aqueous hydrochloric acid solution was then added, and the mixture was stirred at a temperature below 10° C. for 2 h. The organic layer was separated and the aqueous layer was extracted with 2-MeTHF. The organic layers were combined and successively washed with 10% aqueous sodium chloride solution, 10% aqueous sodium hydrogencarbonate solution and 10% aqueous sodium chloride solution. 1-butanol (40 ml) was added to the organic layer and THF and 2-MeTHF were evaporated under vacuum at a temperature below 50° C. The remaining mixture in 1-butanol was cooled to 5° C. The precipitate was filtered, washed with water and dried under vacuum to afford crude 17α-ethynyl-17β-hydroxy-18-methyl-estra-4,15-dien-3-one (14.9 g, yield: 75%).

Workup

  1. customwithout exceeding 25° C
  2. temperaturecooled to 7° C.
  3. stirringThe mixture was stirred for 10 min
  4. stirringthe mixture was stirred at a temperature below 10° C. for 2 h
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with 2-MeTHF
  7. washsuccessively washed with 10% aqueous sodium chloride solution, 10% aqueous sodium hydrogencarbonate solution and 10% aqueous sodium chloride solution
  8. addition1-butanol (40 ml) was added to the organic layer and THF and 2-MeTHF
  9. customwere evaporated under vacuum at a temperature below 50° C
  10. temperatureThe remaining mixture in 1-butanol was cooled to 5° C
  11. filtrationThe precipitate was filtered
  12. washwashed with water
  13. customdried under vacuum

Sources & evidence

ORD record
ord-83d922c0af6047dfa27cfbe208244987
Source dataset
uspto-grants-2015_04
Patent number
US09012667B2

Reaction notes

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