Phosphorus oxychloride → 1-(2,4-difluorophenyl)-1-(4-(4-cyanothiazol-2-yl)-thiophen-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol

HRID 482069Notes

Reaction equation

HRID 482069 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[S:18][CH:19]=[C:20]([C:22]2[S:23][CH:24]=[C:25]([C:27](=O)[NH2:28])[N:26]=2)[CH:21]=1)([OH:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[S:18][CH:19]=[C:20]([C:22]2[S:23][CH:24]=[C:25]([C:27]#[N:28])[N:26]=2)[CH:21]=1)([OH:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 190651561-(2,4-difluorophenyl)-1-(4-(4-carbamoylthiazol-2-yl)-thiophen-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol

Product 1

HCID 190651511-(2,4-difluorophenyl)-1-(4-(4-cyanothiazol-2-yl)-thiophen-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanolYield 69.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1-(2,4-Difluorophenyl)-1-(4-(4-carbamoylthiazol-2-yl)-thiophen-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol (1.2 g) was dissolved in pyridine (7.1 ml). The solution was cooled on an ice bath, and phosphorus oxychloride (0.29 ml) was added thereto. The resultant mixture was stirred for 30 minutes. After the reaction, the reaction mixture was added with saline and extracted with ethyl acetate. An organic layer was washed once with 6N hydrochloric acid (20 ml) and then each once with water, a saturated aqueous solution of sodium hydrogencarbonate and saturated saline. After the thus-washed organic layer was dried over magnesium sulfate, the solvent was distilled out, and the residue was purified by chromatography on silica gel. Recrystallization from a solution of dichloromethane in ether was further conducted to obtain a solid (800 mg). Melting point: 172°-173° C.

Workup

  1. temperatureThe solution was cooled on an ice bath
  2. customAfter the reaction
  3. additionthe reaction mixture was added with saline
  4. extractionextracted with ethyl acetate
  5. washAn organic layer was washed once with 6N hydrochloric acid (20 ml)
  6. dry with materialAfter the thus-washed organic layer was dried over magnesium sulfate
  7. distillationthe solvent was distilled out
  8. customthe residue was purified by chromatography on silica gel
  9. customRecrystallization from a solution of dichloromethane in ether

Sources & evidence

ORD record
ord-ea86a9cd25444be08447b52e974f66cd
Source dataset
uspto-grants-1998_08
Patent number
US05792781

Reaction notes

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