Hydrochloric Acid → HCID 20079605, compound

HRID 1654226Notes

Reaction equation

HRID 1654226 reaction equation
[SH:1]CCC(OC)=O.[H-].[Na+].[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[C:18]1([CH:21]([N:23]2[CH:27]=[N:26][CH:25]=[N:24]2)[CH3:22])[CH2:20][O:19]1.Cl>CN(C)C=O.O>[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[C:18]([OH:19])([CH:21]([N:23]1[CH:27]=[N:26][CH:25]=[N:24]1)[CH3:22])[CH2:20][SH:1]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 18050Methyl 3-mercaptopropionateHCID 24758Sodium hydrideHCID 21461141HCID 21461141, compound

Product 1

HCID 20079605HCID 20079605, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

Methyl 3-mercaptopropionate (0.88 ml) was added to N,N-dimethylformamide (14 ml) containing 60% sodium hydride in oil (0.32 g) under ice-cooling. After 5 minutes, a solution of 2-(2,4-difluorophenyl)-2-[1-(1H-1,2,4-triazol-1-yl)ethyl]oxirane (0.67 g) in N,N-dimethylformamide (3.5 ml) was added over 5 minutes with ice-cooling. After 15 minutes, the reaction mixture was poured into water (150 ml), neutralized with hydrochloric acid and extracted with ethyl acetate (50 ml×3). The organic layers were combined, washed with saturated aqueous sodium chloride solution (30 ml× 2), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (3 cm×10 cm) and elution was carried out with ethyl acetate-hexane (1:1). The desired fraction was concentrated and diethyl ether was added to the residue to give crude crystals (0.25 g) of 2-(2,4-difluorophenyl)-1-mercapto-3-[(1H)-1,2,4-triazol-1-yl]-2-butanol (of low polarity; compound 116, diastereomer B). The crystals were recrystallized from a mixture of chloroform and diethyl ether to give 0.21 g of compound 116. The mother liquor of the above crude crystals was further subjected to silica gel chromatography (2 cm×12 cm) and elution was carried out with ethyl acetate-hexane (1:1). The desired fraction was concentrated and diethyl ether and hexane were added to the residue to give crude crystals (0.25 g) of 2-(2,4-difluorophenyl)-1-mercapto-3-[(1H)-1,2,4-triazol-1-yl]-2-butanol (of high polarity; compound 115, diastereomer A). The crystals were recrystallized from a mixture of chloroform and diethyl ether to give crystals of compound 115 (0.11 g). Compound 115 (diastereomer A) m.p. 112°-117° C. (colorless prism)

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. waitAfter 15 minutes
  4. extractionextracted with ethyl acetate (50 ml×3)
  5. washwashed with saturated aqueous sodium chloride solution (30 ml× 2)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washThe residue was subjected to silica gel chromatography (3 cm×10 cm) and elution
  9. concentrationThe desired fraction was concentrated
  10. additiondiethyl ether was added to the residue
  11. customto give crude crystals (0.25 g) of 2-(2,4-difluorophenyl)-1-mercapto-3-[(1H)-1,2,4-triazol-1-yl]-2-butanol (of low polarity; compound 116, diastereomer B)
  12. customThe crystals were recrystallized from a mixture of chloroform and diethyl ether

Sources & evidence

ORD record
ord-02d51e393c8b4ebe9f9f250712c66f4a
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

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