Sodium hydride → 1-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-

HRID 731022Notes

Reaction equation

HRID 731022 reaction equation
[H-].[Na+].Cl[CH2:4][C@:5]([C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])([OH:9])[C@H:6](O)[CH3:7].C1(C)C=CC(S([N:27]2[CH:31]=[N:30][CH:29]=[N:28]2)(=O)=O)=CC=1.N1C=CN=N1>CN(C=O)C.O>[F:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[C@@:5]1([CH2:4][N:27]2[CH:31]=[N:30][CH:29]=[N:28]2)[C@H:6]([CH3:7])[O:9]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 35054241-(p-Toluenesulfonyl)-1,2,4-triazoleHCID 67175587(2R,3R)-1-Chloro-2-(2,4-difluorophenyl)butane-2,3-diolHCID 178418936HCID 178418936, compound

Product 1

HCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-Yield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

First, 0.21 g (5.10 mmol) of sodium hydride (60% content) was suspended in 3 mL of DMF, and the resulting suspension was cooled in ice. A solution of 0.53 g (2.19 mmol) of (2R,3R)-1-chloro-2-(2,4-difluorophenyl)butane-2,3-diol in 5 mL of DMF was added thereto, and stirring was performed for 1 hour. A solution of 0.64 g (2.85 mmol) of 1-(p-toluenesulfonyl)-1,2,4-triazole and 0.06 g (0.88 mmol) of triazole in 3 mL of DMF was added, and the reaction solution was stirred at 60° C. for 3 hours. Then, the resulting solution was cooled to room temperature, and 10 mL of water was added to stop the reaction. The resulting product was extracted with ethyl acetate (20 mL×2), and concentration was performed under reduced pressure. A quantitative analysis was performed by HPLC. Thereby, the title compound was obtained in a yield of 43% (HPLC conditions, column: CAPCELL PAK C18 TYPE MG manufactured by Shiseido Co. Ltd., mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=2/8, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 37 minutes). 1H-NMR (400 MHz, CDCl3) δ: 1.64 (d, 3H, J=5.6 Hz), 3.19 (q, 1H, J=5.6 Hz), 4.42 (d, 1H, J=14.6 Hz), 4.87 (d, 1H, J=14.6 Hz), 6.69-6.80 (m, 2H), 6.98-7.03 (m, 1H), 7.81 (s, 1H), 7.98 (s, 1H).

Workup

  1. temperaturethe resulting suspension was cooled in ice
  2. stirringthe reaction solution was stirred at 60° C. for 3 hours
  3. customthe reaction
  4. extractionThe resulting product was extracted with ethyl acetate (20 mL×2), and concentration

Sources & evidence

ORD record
ord-aaef3a1a28fe41009c284ea4b708b126
Source dataset
uspto-grants-2009_09
Patent number
US07582781B2

Reaction notes

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