Ammonia → HCID 56631149, compound

HRID 1659834Notes

Reaction equation

HRID 1659834 reaction equation
[Li].N.[O:3]1[C@H:5]2[C:6](=[O:27])[CH:7]=[C:8]3[C@:24]([CH3:25])([C@@H:4]12)[C@@H:23]1[C@H:11]([C@H:12]2[C@:20]([CH3:26])([CH2:21][CH2:22]1)[C@@H:15]([C@H:16]([CH3:19])[CH2:17][OH:18])[CH2:14][CH2:13]2)[CH:10]=[CH:9]3.C=CC(=C)C.[Cl-].[NH4+]>CCOCC.O1CCCC1.CCOCC>[OH:3][C@@H:4]1[C@@:24]2([CH3:25])[C:8](=[CH:9][CH2:10][C@@H:11]3[C@@H:23]2[CH2:22][CH2:21][C@@:20]2([CH3:26])[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[C@H:16]([CH3:19])[CH2:17][OH:18])[CH2:7][C@@H:6]([OH:27])[CH2:5]1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6557IsopreneHCID 25517Ammonium Chloride5×HCID 3028194Lithium7×HCID 13044100HCID 13044100, compound

Product 1

HCID 56631149HCID 56631149, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21868444Ether tetrahydrofuranSolvent

Procedure

0.334 g (48 mg-atom) of lithium are added while stirring and gassing with argon to 170 ml of dry liquid ammonia at -31° C. to -33° C. The resulting dark blue mixture is stirred for 15 minutes and then treated dropwise within 40 minutes with a solution of 3.0 g (8.76 mmol) of (20S)-1α,2α-epoxy-21-hydroxy-20-methyl-pregna-4,6-dien-3-one in 208 ml of ether/tetrahydrofuran (4.2:1). After stirring for an additional 15 minutes, 0.2 ml of isoprene are added to the blue mixture and the resulting pink mixture is subsequently treated, while stirring and gassing with argon, first with 3.045 g (57 mmol) of ammonium chloride in portions and then with 0.0608 g (8.7 mg-atom) of lithium. As soon as the lithium has dissolved, 0.468 g (8.7 mmol) of ammonium chloride and then a further 0.0608 g (8.7 mg-atom) of lithium are added. This procedure, i.e. the addition of 8.7 mmol of ammonium chloride followed by 8.7 mg-atom of lithium, is repeated a further fourteen times, for which a total of 6.552 g (122 mmol) of ammonium chloride and 0.851 g (122 mg-atom) of lithium are required. As soon as the lithium of the last addition has dissolved, 10.8 g (180 mmol) of ammonium chloride and then 150 ml of ether are added, and the ammonia is evaporated with stirring. The resulting suspension is diluted at 0° C. with 200 ml of water and extracted with ethyl acetate. The extract is washed with saturated sodium chloride solution, dried over sodium sulphate and evaporated at 40° C./11 Torr. Chromatography of the residue on 90 g of silica gel with benzene/ethyl acetate (1:1) and ethyl acetate yields 1.93 g (63%) of uniform, crystalline (20S)-1α,3β,21-trihydroxy-20-methyl-pregn-5-ene of melting point 205°-207° C.; [α]D25 =-25.8° (c=0.5 in methanol). The analytical sample is prepared by recrystallisation from acetone; melting point 206°-208° C., [α]D25 =-27° (c=0.5 in methanol).

Workup

  1. stirringThe resulting dark blue mixture is stirred for 15 minutes
  2. stirringAfter stirring for an additional 15 minutes
  3. additionthe resulting pink mixture is subsequently treated
  4. stirringwhile stirring
  5. dissolutionhas dissolved
  6. customthe ammonia is evaporated
  7. stirringwith stirring
  8. additionThe resulting suspension is diluted at 0° C. with 200 ml of water
  9. extractionextracted with ethyl acetate
  10. washThe extract is washed with saturated sodium chloride solution
  11. dry with materialdried over sodium sulphate
  12. customevaporated at 40° C./11 Torr

Sources & evidence

ORD record
ord-a0a3fddc1867419fbf6e09b5f4817650
Source dataset
uspto-grants-1981_12
Patent number
US04305881

Reaction notes

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