Hydrochloric Acid → Gestodene

HRID 1679766Notes

Reaction equation

HRID 1679766 reaction equation
[CH:1]#[CH:2].[CH2:3]([Li])[CH2:4][CH2:5][CH3:6].C[C@:9]12[CH2:25][CH2:24][C@H:23]3[C@@H:14]([CH2:15][CH2:16][C:17]4[CH2:18][CH2:19]CC[C:22]=43)[C@@H:13]1[CH:12]=[CH:11][C:10]2=[O:26].[Cl-].[NH4+].C[C@]12CC[C@H]3[C@@H](CCC4CCCCC=43)[C@@H]1C=C[C@@H]2[OH:47].Cl>C(OCC)(=O)C.CC(C)=O.O1CCCC1>[C:1]([C@:3]1([OH:47])[CH:9]=[CH:25][C@H:24]2[C@H:23]3[C@H:14]([CH2:15][CH2:16][C@:4]12[CH2:5][CH3:6])[C@@H:13]1[C:18](=[CH:19][C:10](=[O:26])[CH2:11][CH2:12]1)[CH2:17][CH2:22]3)#[CH:2]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6326AcetyleneHCID 25517Ammonium ChlorideHCID 22798512HCID 22798512, compoundHCID 22802596HCID 22802596, compoundHCID 178418339Butyllithium

Product 1

HCID 3033968Gestodene

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Acetylene is passed for about 45 minutes through a solution, cooled with ice water, of 100 ml. of n-butyllithium (approximately 15% strength in hexane) in 350 ml. of tetrahydrofuran. Thereafter, 10.0 g. of 18-methyl-3,3-(2',2'-dimethyl-1',3'-propylenedioxy)-5 and -5(10),15-estradien-17-one in 100 ml. of tetrahydrofuran is added dropwise thereto under agitation. After 30 minutes, the solution is combined with saturated ammonium chloride solution, diluted with ethyl acetate, washed neutral with water, and dried over sodium sulfate. The solution is concentrated to dryness under vacuum, thus obtaining 11.4 g. of crude 17α-ethynyl-18-methyl-3,3-(2',2'-dimethyl-1',3'-propylenedioxy)-5 and -5(10),15-estradien-17β-ol, which is suspended in 70 ml. of acetone. This reaction mixture is combined with 0.1 ml. of concentrated hydrochloric acid, stirred for 2 hours at room temperature, and then the solution is poured into ice water. The thus-precipitated product is vacuum-filtered, dissolved in ethyl acetate, and dried over sodium sulfate. After chromatographing the crude product on silica gel with 20% acetone-hexane, the product is 4.8 g. of 17α-ethynyl-17β-hydroxy-18-methyl-4,15-estradien-3-one, m.p. 199°-200°.

Workup

  1. washwashed neutral with water
  2. dry with materialdried over sodium sulfate
  3. concentrationThe solution is concentrated to dryness under vacuum
  4. customthus obtaining 11.4 g
  5. filtrationThe thus-precipitated product is vacuum-filtered
  6. dissolutiondissolved in ethyl acetate
  7. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-9c4a8704b219466bb70f1dcd58540b7c
Source dataset
uspto-grants-1978_03
Patent number
US04081537

Reaction notes

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