Ammonia → HCID 57011210, compound

HRID 1659839Notes

Reaction equation

HRID 1659839 reaction equation
[Li].N.[O:3]1[C@H:5]2[C:6](=[O:32])[CH:7]=[C:8]3[C@:29]([CH3:30])([C@@H:4]12)[C@@H:28]1[C@H:11]([C@H:12]2[C@:25]([CH3:31])([CH2:26][CH2:27]1)[C@@H:15]([C@H:16]([O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[CH3:17])[CH2:14][CH2:13]2)[CH:10]=[CH:9]3.C=CC(=C)C.[Cl-].[NH4+]>CCOCC>[OH:3][C@@H:4]1[C@@:29]2([CH3:30])[C:8](=[CH:9][CH2:10][C@@H:11]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[C@H:16]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH3:17])[CH2:7][C@@H:6]([OH:32])[CH2:5]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 6557IsopreneHCID 25517Ammonium Chloride5×HCID 3028194Lithium7×HCID 57286567HCID 57286567, compound

Product 1

HCID 57011210HCID 57011210, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

0.316 g (45 mg-atom) of lithium are added to 150 ml of dry liquid ammonia at -31° C. to -33° C. After stirring for 15 minutes in an argon atmosphere, the resulting dark blue mixture is treated dropwise within 45 minutes with a solution of 3.23 g (7.8 mmol) of (20R)-1α,2α-epoxy-20-[(tetrahydro-2H-pyran-2-yl)oxy]-pregna-4,6-dien-3-one in 180 ml of ether. The blue mixture is stirred at the aforementioned temperature for 15 minutes in an argon atmosphere and 0.15 ml of isoprene is added. The resulting pink mixture is treated with 2.845 g (53 mmol) of ammonium chloride in portions and then with 0.0527 g (7.6 mg-atom) of lithium. As soon as the lithium has dissolved, 0.4065 g (7.6 mmol) of ammonium chloride and subsequently a further 0.0527 g (7.6 mg-atom) of lithium are added. This procedure, i.e. the addition of 7.6 mmol of ammonium chloride followed by 7.6 mg-atom of lithium, is repeated a further fourteen times, for which a total of 5.691 g (106 mmol) of ammonium chloride and 0.7378 g (106 mg-atom) of lithium are required. After the lithium of the last addition has dissolved, 10.0 g (180 mmol) of ammonium chloride and 200 ml of ether are added, and 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 65 g of silica gel with hexane/ether (1:1) gives 2.52 g (78%) of uniform (20R)-1α,3β-dihydroxy-20-[(tetrahydro-2H-pyran-2-yl)oxy]-pregn-5-ene of melting point 122°-124° C.; [α]D25 =-42° (c=1.0 in chloroform). By acidic hydrolysis there is obtained (20R)-1α,3β,20-trihydroxy-pregn-5-ene of melting point 235°-237° C.; [α]D25 =43° (c=0.5 in methanol).

Workup

  1. additionis added
  2. dissolutionhas dissolved
  3. customammonia is evaporated
  4. stirringwith stirring
  5. additionThe resulting suspension is diluted at 0° C. with 200 ml of water
  6. extractionextracted with ethyl acetate
  7. washThe extract is washed with saturated sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. customevaporated at 40° C./11 Torr

Sources & evidence

ORD record
ord-a554177e96054e40ae692c2bdefb309e
Source dataset
uspto-grants-1981_12
Patent number
US04305881

Reaction notes

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