Hydrochloric Acid → HCID 15069850, compound

HRID 1709160Notes

Reaction equation

HRID 1709160 reaction equation
[CH3:1][C@@:2]12[C@H:12]3[C@H:13]([OH:26])[CH2:14][C@:15]4([CH3:25])[C@@:19]([OH:24])([C:20]([CH2:22][OH:23])=[O:21])[CH2:18][CH2:17][C@H:16]4[C@@H:11]3[CH2:10][CH2:9][C:8]1=[CH:7][C:5](=[O:6])[CH2:4][CH2:3]2.[C:27]([CH2:31][C:32](Cl)=[O:33])([CH3:30])([CH3:29])[CH3:28].Cl.[C:36](=[O:39])(O)[O-:37].[K+].[C:41](=[O:44])(O)[O-].[Na+].N1C=CC=[CH:48][CH:47]=1>CC(C)=O.CO>[C:36]([CH2:47][CH2:48][C:41](=[O:44])[O:23][CH2:22][C:20](=[O:21])[C@:19]1([OH:24])[C@:15]2([CH3:25])[C@H:16]([C@H:11]3[C@H:12]([C@H:13]([O:26][C:32](=[O:33])[CH2:31][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:14]2)[C@:2]2([CH3:1])[C:8](=[CH:7][C:5](=[O:6])[CH:4]=[CH:3]2)[CH2:9][CH2:10]3)[CH2:17][CH2:18]1)([OH:37])=[O:39]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 815143,3-Dimethylbutanoyl chlorideHCID 22986011-EpicortisolHCID 516892Sodium BicarbonateHCID 516893Potassium Bicarbonate

Product 1

HCID 15069850HCID 15069850, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Procedure

The A1-, 17,21-acetonide of 11-epi-cortisol (4.90g) was dissolved in 25 ml of pyridine and reacted with 2.40 g of t-butylacetyl chloride for 6 hours at room temperature under nitrogen. The mixture was partitioned between ether and aqueous sodium bicarbonate. The organic phase washed with brine and was dried over sodium sulfate and concentrated. The residue was chromatographed on silica gel with 40/60 ethyl acetate hexane to yield 3.87 g of TLC pure product. This material was dissolved in 200 ml of acetone. To this solution was added 10 ml of 10% aqueous HCl. The mixture was stirred for 48 hours. The reaction was concentrated. The residue was partitioned between methylene chloride and aqueous sodium bicarbonate. The organic phase was dried over sodium sulfate and concentrated. The 3.55 g residue. This residue was dissolved in 20 ml of DMF and was reacted with 1.00 g of succinic anhydride and a trace of potassium bicarbonate at room temperature for 20 h. The reaction was concentrated. The residue was chromatographed on silica gel (4% methanol in methylene chloride to 4% methanol/.5% HOAc in methylene chloride) to yield 4.01 g of the hemisuccinate. This was dissolved in methanol and reacted with an aqueous solution of 0.60 g of sodium bicarbonate. The solution was lyophilized. The residue was triturated with acetone and ether to yield 2.14 g of product which was 98.6% pure by hplc, decomp 220. Anal. Calcd for C31H41O9Na.H20. Calcd/Found: C, 62.20/55.69; H, 7.24/ 6.18; H20, 3.01/2.24. m/e=581.

Workup

  1. customThe mixture was partitioned between ether and aqueous sodium bicarbonate
  2. washThe organic phase washed with brine
  3. dry with materialwas dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel with 40/60 ethyl acetate hexane
  6. customto yield 3.87 g of TLC pure product
  7. concentrationThe reaction was concentrated
  8. customThe residue was partitioned between methylene chloride and aqueous sodium bicarbonate
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. concentrationconcentrated
  11. dissolutionThis residue was dissolved in 20 ml of DMF
  12. customwas reacted with 1.00 g of succinic anhydride
  13. concentrationThe reaction was concentrated
  14. customThe residue was chromatographed on silica gel (4% methanol in methylene chloride to 4% methanol/.5% HOAc in methylene chloride)
  15. customto yield 4.01 g of the hemisuccinate
  16. customThe residue was triturated with acetone and ether

Sources & evidence

ORD record
ord-55738b0a6d434fae80e5192bc6a993b0
Source dataset
uspto-grants-1990_08
Patent number
US04948533

Reaction notes

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