Diethyl Ether → Gestodene

HRID 1679764Notes

Reaction equation

HRID 1679764 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:6]#[CH:7].[CH3:8][C@:9]12[CH2:25][CH2:24][C@H:23]3[C@@H:14]([CH2:15][CH2:16][C:17]4[CH2:18]CCC[C:22]=43)[C@@H:13]1[CH:12]=CC2=O.[Cl-].[NH4+].CC[O:31][CH2:32][CH3:33]>>[C:6]([C@:5]1([OH:1])[CH:18]=[CH:17][C@H:22]2[C@H:23]3[C@H:14]([CH2:15][CH2:16][C@:4]12[CH2:3][CH3:2])[C@@H:13]1[C:9](=[CH:8][C:32](=[O:31])[CH2:33][CH2:12]1)[CH2:25][CH2:24]3)#[CH:7]

Participants

6

Reactant 5

HCID 3283Diethyl EtherHCID 6326AcetyleneHCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 22798512HCID 22798512, compound

Product 1

HCID 3033968Gestodene

Procedure

7.5 g. of magnesium filings is reacted in 140 ml. of tetrahydrofuran with 24 ml. of ethyl bromide to obtain ethylmagnesium bromide. To this Grignard solution is added 300 ml. of tetrahydrofuran, and under ice cooling acetylene is passed through the solution for about 40 minutes. Then, a solution of 5 g. of 18-methyl-3,3-(2',2'-dimethyl-1',3'-propanediol)-5-and -5(10),15-estradien-17-one in 200 ml. of tetrahydrofuran is added dropwise to the reaction solution, and the latter is agitated at room temperature. After 2 hours, the solution is carefully combined with an ammonium chloride solution and diluted with ether. The organic phase is washed repeatedly with water, dried over sodium sulfate, and evaporated to dryness under vacuum. After chromatographing the crude product on silica gel with 2.5-2.9% acetone-hexane, the yield is 3.1 g. of 17α-ethynyl-18-methyl-3,3-(2',2'-dimethyl-1',3'-propylenedioxy)-5,15 and -5(10),15-estradien-17β-ol; these compounds are agitated under reflux in 70 ml. of methanol and 14 ml. of water with 2.3 g. of oxalic acid for 40 minutes. The solution is diluted with ether, washed neutral with water, dried, and treated with activated carbon. After recrystallization from acetone-hexane, 1.4 g. of 17α-ethynyl-17β-hydroxy-18-methyl-4,15-estradien-3-one is obtained; m.p. 197.9°.

Workup

  1. additionTo this Grignard solution is added 300 ml
  2. waitAfter 2 hours
  3. washThe organic phase is washed repeatedly with water
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness under vacuum
  6. stirringthese compounds are agitated
  7. temperatureunder reflux in 70 ml
  8. waitof oxalic acid for 40 minutes
  9. additionThe solution is diluted with ether
  10. washwashed neutral with water
  11. customdried
  12. additiontreated with activated carbon
  13. customAfter recrystallization from acetone-hexane, 1.4 g

Sources & evidence

ORD record
ord-7131405e7bd948ca818ae81d481df950
Source dataset
uspto-grants-1978_03
Patent number
US04081537

Reaction notes

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