Formaldehyde → HCID 54425312, compound

HRID 1285311Notes

Reaction equation

HRID 1285311 reaction equation
[CH3:1][C:2]1[C:19]2[C@:14]([CH3:21])([CH2:15][CH2:16][C:17](=[O:20])[CH:18]=2)[C@@H:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][CH2:12]2)([CH3:10])[C:8](=[O:22])[CH2:7][CH2:6]3)[CH:3]=1.[CH3:23]OC(=O)C(OC)=O.C[O-].[Na+].C=O>C1COCC1.CO.C(N(CC)CC)C.C(O)(=O)C>[CH3:1][C:2]1[C:19]2[C@:14]([CH3:21])([CH2:15][CH2:16][C:17](=[O:20])[CH:18]=2)[C@@H:13]2[C@H:4]([C@H:5]3[C@@:9]([CH2:11][CH2:12]2)([CH3:10])[C:8](=[O:22])[C:7](=[CH2:23])[CH2:6]3)[CH:3]=1

Participants

9

Reactant 4

HCID 712FormaldehydeHCID 11120Dimethyl oxalateHCID 10494334HCID 10494334, compoundHCID 10942334Sodium Methoxide

Product 1

HCID 54425312HCID 54425312, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

6-Methylandrosta-4,6-diene-3,17-dione (IA, U.S. Pat. No. 3,177,966, Example 16, 3.0 g) was dissolved in THF (32 ml) and dimethyloxalate (1.64 g) was added. The mixture was cooled under nitrogen to 0°. Sodium methoxide in methanol (25%, 2.75 ml) was added dropwise. The mixture was stirred approximately 2 hrs. at 0°; then neutralized with acetic acid (0.12 ml). Triethylamine (1.2 ml) and methanol (5.0 ml) were added followed by formaldehyde solution (37%, 1.13 ml). Following addition of all the reactants, the ice bath was removed and the reaction stirred at 20°-25° for 1.5 hrs. Water (50 ml) was added, followed by ethyl acetate and methyl t-butyl ether. These phases were separated and the organic phase was washed twice with saline. The combined aqueous layers were back extracted once with ethyl acetate and the combined organic extracts were dried over sodium sulfate after the addition of some methylene chloride. The mixture was filtered through Celite and the filtrate removed under reduced pressure to give an oil which was chromatographed over silica gel (230-400 mesh, 140 g). The appropriate fractions were pooled and concentrated to give the title compound.

Workup

  1. temperatureThe mixture was cooled under nitrogen to 0°
  2. customat 0°
  3. additionaddition of all the reactants
  4. customthe ice bath was removed
  5. stirringthe reaction stirred at 20°-25° for 1.5 hrs
  6. additionWater (50 ml) was added
  7. customThese phases were separated
  8. washthe organic phase was washed twice with saline
  9. extractionThe combined aqueous layers were back extracted once with ethyl acetate
  10. dry with materialthe combined organic extracts were dried over sodium sulfate
  11. additionafter the addition of some methylene chloride
  12. filtrationThe mixture was filtered through Celite
  13. customthe filtrate removed under reduced pressure
  14. customto give an oil which
  15. customwas chromatographed over silica gel (230-400 mesh, 140 g)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-9d9c5172bab540b2bda42cea974accbd
Source dataset
uspto-grants-1986_01
Patent number
US04567001

Reaction notes

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