Hydrochloric Acid → HCID 69735993, compound

HRID 1063446Notes

Reaction equation

HRID 1063446 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[CH:5]([CH3:11])[C:6]([O:8]CC)=[O:7])[CH3:2].[H-].[Na+].I[CH2:16][CH2:17][C:18]1[S:19][CH:20]=[C:21]([C:23]#[C:24][CH2:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:22]=1.Cl.[OH-].[K+]>CN(C)C=O.C(O)C.O>[CH2:1]([O:3][C:4](=[O:12])[C:5]([CH2:16][CH2:17][C:18]1[S:19][CH:20]=[C:21]([C:23]#[C:24][CH2:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:22]=1)([CH3:11])[C:6]([OH:8])=[O:7])[CH3:2]

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 11857Diethyl methylmalonateHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 22279923HCID 22279923, compound

Product 1

HCID 69735993HCID 69735993, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Methylmalonic acid diethylester (1.57 g, 9.02 mmol) was dissolved in dimethylformamide (30 ml), and sodium hydride (0.38 g, 9.47 mmol) was added thereto in an ice bath, and then the mixture was stirred for 1 hour at room temperature in a nitrogen atmosphere. The dimethylformamide solution (30 ml) of 2-(2-iodoethyl)-4-(5-phenylpent-1-ynyl)thiophene obtained in Example 25 (e) was added dropwise to the reaction solution in an ice bath, and the mixture was stirred for 4 hours at room temperature under a nitrogen atmosphere. After the reaction solution was cooled down, acidified with 1N hydrochloric acid, and the resulting solution was extracted with ethyl acetate, and then the ethyl acetate layer was washed with a 1N aqueous sodium hydroxide solution and then with a saturated aqueous sodium chloride solution. The ethyl acetate layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The residue was partially purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=50:1-20:1). The obtained mixture was dissolved in a mixture of ethanol (9 ml) and water (1 ml), and potassium hydroxide (0.80 g, 14.3 mmol) was added thereto in an ice bath, and then the reaction mixture was stirred for 3 days at room temperature. After the reaction solution was acidified with 1N hydrochloride acid, the resulting solution was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The residue was purified by chromatography on a silica gel column (elution solvent; dichloromethane:methanol=50:1) to afford the title compound (1.02 g, 28% yield).

Workup

  1. stirringthe mixture was stirred for 4 hours at room temperature under a nitrogen atmosphere
  2. temperatureAfter the reaction solution was cooled down
  3. extractionthe resulting solution was extracted with ethyl acetate
  4. washthe ethyl acetate layer was washed with a 1N aqueous sodium hydroxide solution
  5. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  6. customthe solvent was evaporated in vacuo
  7. customThe residue was partially purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=50:1-20:1)
  8. additionwas added
  9. stirringin an ice bath, and then the reaction mixture was stirred for 3 days at room temperature
  10. extractionthe resulting solution was extracted with ethyl acetate
  11. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  12. customthe solvent was evaporated in vacuo
  13. customThe residue was purified by chromatography on a silica gel column (elution solvent; dichloromethane:methanol=50:1)

Sources & evidence

ORD record
ord-2bf69fcf4d744484b2f159662428e905
Source dataset
uspto-grants-2005_11
Patent number
US06964976B2

Reaction notes

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