Ammonia → HCID 53905859, compound

HRID 1659841Notes

Reaction equation

HRID 1659841 reaction equation
[Li].N.[CH2:3]1[CH2:27][O:26][C:5]2([CH2:10][CH2:9][C@H:8]3[C@H:11]4[C@H:21]([CH2:22][CH2:23][C@:6]23[CH3:7])[C@:19]2([CH3:20])[C:14](=[CH:15][C:16](=[O:25])[C@@H:17]3[O:24][C@@H:18]32)[CH:13]=[CH:12]4)[O:4]1.C=CC(=C)C.[Cl-].[NH4+]>CCOCC.O1CCCC1.CCOCC>[CH2:27]1[CH2:3][O:4][C:5]2([CH2:10][CH2:9][C@H:8]3[C@H:11]4[C@H:21]([CH2:22][CH2:23][C@:6]23[CH3:7])[C@:19]2([CH3:20])[C:14]([CH2:15][C@@H:16]([OH:25])[CH2:17][C@@H:18]2[OH:24])=[CH:13][CH2:12]4)[O:26]1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6557IsopreneHCID 25517Ammonium Chloride5×HCID 3028194Lithium7×HCID 23631321HCID 23631321, compound

Product 1

HCID 53905859HCID 53905859, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21868444Ether tetrahydrofuranSolvent

Procedure

1.543 g (0.22 g-atom) of lithium are added to 1.3 liters of dry liquid ammonia at -31° C. to -33° C. with stirring in an argon atmosphere. After 5 minutes, there is added dropwise during 40 minutes to the resulting dark blue mixture a solution of 10.83 g (0.0316 mol) of 17,17-ethylenedioxy-1α,2α-epoxyandrosta-4,6-dien-3-one in 765 ml of ether/tetrahydrofuran (2:1). After stirring for 15 minutes, 5.3 ml of isoprene are added dropwise to the mixture. The resulting yellow mixture is treated with stirring with 13.49 g (0.252 mol) of ammonium chloride in portions and then 0.22 g (0.0316 g-atom) of lithium is added. As soon as the lithium has dissolved, 1.69 g (0.0316 mol) of ammonium chloride and subsequently a further 0.22 g (0.0316 g-atom) of lithium are added. This procedure, i.e. the addition of 0.0316 mol of ammonium chloride and 0.0316 g-at of lithium, is repeated a further fourteen times, for which a total of 23.66 g (0.442 mol) of ammonium chloride and 3.08 g (0.442 g-atom) of lithium are required. As soon as the lithium of the last addition has dissolved, 24 g (0.44 mol) of ammonium chloride are added and the mixture is cautiously diluted with 1 liter of ether. Ammonia is evaporated while stirring until an internal temperature of 0° C. has been reached and the remaining suspension is treated with 1 liter of water. The organic phase is separated, the aqueous phase is back-extracted with ethyl acetate, the organic phases are combined, washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated at 40° C./11 Torr. Chromatography of the residue on 300 g of silica gel with benzene/ethyl acetate (3:2) and benzene/ethyl acetate (2:3) gives 8.8 g (80%) of uniform, crystalline 17,17-ethylenedioxy-1α,3β-dihydroxy-androst-5-ene. The analytical sample is obtained by recrystallisation from methanol; white needles of melting point 205°-206° C.; [α]D25 =-89.8° (c=0.5 in chloroform).

Workup

  1. stirringAfter stirring for 15 minutes
  2. additionThe resulting yellow mixture is treated
  3. dissolutionhas dissolved
  4. customAmmonia is evaporated
  5. stirringwhile stirring until an internal temperature of 0° C.
  6. additionthe remaining suspension is treated with 1 liter of water
  7. customThe organic phase is separated
  8. extractionthe aqueous phase is back-extracted with ethyl acetate
  9. washwashed with saturated sodium chloride solution
  10. dry with materialdried over sodium sulphate
  11. customevaporated at 40° C./11 Torr

Sources & evidence

ORD record
ord-f35595426d2841c49732e223644db3e1
Source dataset
uspto-grants-1981_12
Patent number
US04305881

Reaction notes

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