Ammonia → HCID 13044106, compound

HRID 1659833Notes

Reaction equation

HRID 1659833 reaction equation
[O:1]1[C@H:3]2[C:4](=[O:31])[CH:5]=[C:6]3[C@:28]([CH3:29])([C@@H:2]12)[C@@H:27]1[C@H:9]([C@H:10]2[C@:24]([CH3:30])([CH2:25][CH2:26]1)[C@@H:13]([C@H:14]([CH3:23])[CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[CH2:12][CH2:11]2)[CH:8]=[CH:7]3.[Li].N.[Cl-].[NH4+]>CCOCC>[OH:1][C@@H:2]1[C@@:28]2([CH3:29])[C:6](=[CH:7][CH2:8][C@@H:9]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:10]3[CH2:11][CH2:12][C@@H:13]2[C@H:14]([CH3:23])[CH2:15][O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[CH2:5][C@@H:4]([OH:31])[CH2:3]1

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 25517Ammonium Chloride4×HCID 3028194Lithium4×HCID 13044103HCID 13044103, compound

Product 1

HCID 13044106HCID 13044106, compoundYield 87.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 22.4 g (52 mmol, 1 equivalent) of (20S)-1α,2α-epoxy-20-methyl-21-tetrahydropyranyloxy-pregna-4,6-dien-3-one in 1.25 liters of absolute ether is added dropwise within 45 minutes while stirring in an argon atmoshere at -33° C. to a solution of 1.453 g (0.21 g-atom), 4 equivalents) of lithium in 2.1 liters of liquid ammonia. In so doing, when the resulting mixture is only just light blue in colour, the dropwise addition is interrupted briefly and 0.363 g (52.3 mg-atom), 1 equivalent) of lithium is added. After completion of the dropwise addition, the mixture is stirred for 15 minutes and the blue colour is removed from the mixture by the addition of 2 ml of isoprene. With stirring there are added in portions 13.98 g (0.26 mol, 5 equivalents) of ammonium chloride. The mixture is treated in portions under argon at -33° C. with 16.048 g (0.30 mol, 5.7 equivalents) of ammonium chloride, and then with 2.082 g (0.3 g-atom, 5.7 equivalents) of lithium and, as soon as these additions have reacted, the same procedure, i.e. the addition of 16.048 g of ammonium chloride followed by 2.082 g of lithium is repeated a further four times. The mixture is treated with 75 g of ammonium chloride and ammonia is evaporated until the temperature of the mixture has reached 0° C. The residue is treated with 0.2 liter of saturated sodium chloride solution and 1 liter of water, extracted with 3 liters of ether and twice with 2.5 liters of ethyl acetate. The extracts are washed twice with 0.5 liter of saturated sodium chloride solution, combined, dried over sodium sulphate and concentrated at 40° C./11 Torr. The residue is dissolved in 75 ml of benzene and added to a column of 340 g of silica gel prepared in hexane/ether (9:1). Elution (a) with 3 liters of hexane/ether (4:1) and 14 liters of hexane/ether (1:1) yield 2.39 g of apolar fractions and (b) with 19 liters of ether yields 19.7 g (86.78%) of crude (20S)-1α,3β-dihydroxy-20-methyl-21-tetrahydropyranyloxy-pregn-5-ene. Recrystallisation from methanol gives white crystals of melting point 138°-141° C.; [α]D25 =-48.8° (c=0.5 in chloroform).

Workup

  1. additionthe dropwise addition
  2. additionAfter completion of the dropwise addition
  3. customthe blue colour is removed from the mixture by the addition of 2 ml of isoprene
  4. stirringWith stirring there
  5. customis evaporated until the temperature of the mixture
  6. customhas reached 0° C
  7. additionThe residue is treated with 0.2 liter of saturated sodium chloride solution and 1 liter of water
  8. extractionextracted with 3 liters of ether and twice with 2.5 liters of ethyl acetate
  9. washThe extracts are washed twice with 0.5 liter of saturated sodium chloride solution
  10. dry with materialdried over sodium sulphate
  11. concentrationconcentrated at 40° C./11 Torr
  12. dissolutionThe residue is dissolved in 75 ml of benzene
  13. additionadded to a column of 340 g of silica gel
  14. customprepared in hexane/ether (9:1)
  15. washElution (a) with 3 liters of hexane/ether (4:1) and 14 liters of hexane/ether (1:1) yield 2.39 g of apolar fractions and (b) with 19 liters of ether

Sources & evidence

ORD record
ord-a2a7dd5b9df64b88a3f34bc048893931
Source dataset
uspto-grants-1981_12
Patent number
US04305881

Reaction notes

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