Dichloromethane → HCID 20637860, compound

HRID 650937Notes

Reaction equation

HRID 650937 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)#[CH:2].[Li]CCCC.[CH3:14][C:15](=[O:36])[C@@H:16]1[C@:33]2([CH3:34])[C@H:19]([C@H:20]3[C@H:30]([CH2:31][CH2:32]2)[C@:28]2([CH3:29])[C@@H:23]([CH2:24][C:25](=[O:35])[CH2:26][CH2:27]2)[CH2:22][CH2:21]3)[CH2:18][CH2:17]1.C(Cl)Cl>C1COCC1>[N:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:1]#[C:2][C@@:25]1([OH:35])[CH2:26][CH2:27][C@@:28]2([CH3:29])[C@H:23]([CH2:22][CH2:21][C@@H:20]3[C@@H:30]2[CH2:31][CH2:32][C@@:33]2([CH3:34])[C@H:19]3[CH2:18][CH2:17][C@@H:16]2[C:15](=[O:36])[CH3:14])[CH2:24]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 92745PREGNANE-3,20-DIONE, (5.BETA.)-HCID 137268EthynylpyridineHCID 178418339Butyllithium

Product 1

HCID 20637860HCID 20637860, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2-ethynylpyridine (270 mg, 2.6 mmol) in dry THF (15 mL) was treated with a n-BuLi (2.5 M in THF, 2.5 mmol, 1 mL) at −60° C. After stirring the mixture at −78° C. for 0.5 hr, a solution of 5β-pregnan-3,20-dione, cyclic 20-(1,2-ethanediyl acetal)170 mg, 047 mmol) in THF (15 mL) was added and the mixture was stirred at −78° C. for 1 hr. The cooling bath was removed and the mixture was quenched with NH4Cl solution (3 mL). The solvent was removed and the residue was then dissolved in acetone (25 mL). After adding 2N HCl (2 mL) the solution was stirred at rt for 15 min. Sat. NaHCO3 soln. was added to neutralize the acid. The solvents were removed and the residue was extracted with EtOAc. The organic layer was washed with water, and brine. After drying over anhyd. MgSO4 the solution was filtered and evaporated to yield the crude product (360 mg). This crude product was then dessolved in a small amount of CH2Cl2 and poured on a column of silica gel. Elution with toluene:acetone mixture (95:5) gave the unreacted ethynlpyridine as a first fraction. Further elution with the same solvent mixture yielded 3β-(2-pyridyl)ethynyl-3α-hydroxy-5β-pregnan-20-one (107 mg) as a colorless solid; mp 192-195° C.; TLC Rf (toluene:acetone 87:13)=0.21.

Workup

  1. stirringthe mixture was stirred at −78° C. for 1 hr
  2. customThe cooling bath was removed
  3. customthe mixture was quenched with NH4Cl solution (3 mL)
  4. customThe solvent was removed
  5. dissolutionthe residue was then dissolved in acetone (25 mL)
  6. additionAfter adding 2N HCl (2 mL) the solution
  7. stirringwas stirred at rt for 15 min
  8. additionwas added
  9. customThe solvents were removed
  10. extractionthe residue was extracted with EtOAc
  11. washThe organic layer was washed with water, and brine
  12. customAfter drying over anhyd
  13. filtrationMgSO4 the solution was filtered
  14. customevaporated
  15. customto yield the crude product (360 mg)
  16. additionpoured on a column of silica gel
  17. washElution with toluene
  18. customacetone mixture (95:5) gave the unreacted ethynlpyridine as a first fraction
  19. washFurther elution with the same solvent mixture

Sources & evidence

ORD record
ord-79dd17ebbbee4efba44beb26f71e7e68
Source dataset
uspto-grants-2001_08
Patent number
US06277838B1

Reaction notes

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