Nitrogen → HCID 68519354, compound

HRID 865811Notes

Reaction equation

HRID 865811 reaction equation
[Cl:1][CH:2]=[CH:3]Cl.N#N.[Li]CCCC.[CH3:12][C:13](=[O:34])[C@@H:14]1[C@:31]2([CH3:32])[C@H:17]([C@H:18]3[C@H:28]([CH2:29][CH2:30]2)[C@:26]2([CH3:27])[C@@H:21]([CH2:22][C:23](=[O:33])[CH2:24][CH2:25]2)[CH2:20][CH2:19]3)[CH2:16][CH2:15]1>C1COCC1>[Cl:1][C:2]#[C:3][C@@:23]1([OH:33])[CH2:24][CH2:25][C@@:26]2([CH3:27])[C@H:21]([CH2:20][CH2:19][C@@H:18]3[C@@H:28]2[CH2:29][CH2:30][C@@:31]2([CH3:32])[C@H:17]3[CH2:16][CH2:15][C@@H:14]2[C:13](=[O:34])[CH3:12])[CH2:22]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 109001,2-Dichloroethylene2×HCID 92745PREGNANE-3,20-DIONE, (5.BETA.)-HCID 178418339Butyllithium

Product 1

HCID 68519354HCID 68519354, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

An attempt was also made to prepare the organometallic reagent with 1,2-dichloroethylene. A 100 mL three-neck flask equipped with a N2 gas bubbler, a thermometer, and a dropping funnel was charged with 1,2-dichloroethylene (cis, Aldrich, 0.16 mL, 2 mmol, mw=97, d=1.28). Dry THF (7 mL) was added, and the solution was cooled to -10° C., n-BuLi (2.5M in THF, 1.6 mL, 4 mmol) was added dropwise over a period of 10 min. The mixture was stirred at -30° C. for 20 min and then at 0°-5° C. for 10 more min. The resulting reagent was then recooled to -30° C. and was treated dropwise with a solution of 5β-pregnan-3,20-dione, 20-ketal (360 mg, 1 mmol) in THF (15 mL). The cooling bath was removed and the mixture was stirred at room temp. for 30 min. (100% conversion as detected by TLC). The cooling bath was removed and the resulting solution was quenched with sat. NH4Cl solution (1 mL). The solvent was removed and the residue was dissolved in acetone (30 mL). After adding 2N HCl (5 mL) the solution was stirred at ambient temperature for 1.5 h. The mixture was neutralized with dil. NaOH solution (pH 5-6). The precipitated solid (429 mg) was collected by filtration, washed with water, and dried. The crude product was then purified by column chromatography over silica gel (toluene acetone 95:5) to yield 3β-chloroethynyl-3α-hydroxy-5β-pregnan-20-one (130 mg); TLC-Rf 0.33 (toluene:acetone 95:5), NMR (CDCl3) δ 0.59 (s, 3H, Me), 0.97 (s, 3H, Me), 2.11 (s, 3H, Me), 2.55 (m, 1H).

Workup

  1. customat 0°-5° C.
  2. customwas then recooled to -30° C.
  3. customThe cooling bath was removed
  4. stirringthe mixture was stirred at room temp. for 30 min. (100% conversion as detected by TLC)
  5. customThe cooling bath was removed
  6. customthe resulting solution was quenched with sat. NH4Cl solution (1 mL)
  7. customThe solvent was removed
  8. dissolutionthe residue was dissolved in acetone (30 mL)
  9. additionAfter adding 2N HCl (5 mL) the solution
  10. stirringwas stirred at ambient temperature for 1.5 h
  11. filtrationThe precipitated solid (429 mg) was collected by filtration
  12. washwashed with water
  13. customdried
  14. customThe crude product was then purified by column chromatography over silica gel (toluene acetone 95:5)

Sources & evidence

ORD record
ord-76a296e62b0e4e64a8842894113089c3
Source dataset
uspto-grants-1996_10
Patent number
US05567830

Reaction notes

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