1-(2,4-Difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone → 6-Chloro-alpha-(2,4-difluorophenyl)-5-fluoro-beta-methyl-alpha-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol

HRID 1197852Notes

Reaction equation

HRID 1197852 reaction equation
[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[C:15]([F:16])=[C:14]([CH2:17][CH3:18])[N:13]=[CH:12][N:11]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[C:27](=[O:34])[CH2:28][N:29]1[CH:33]=[N:32][CH:31]=[N:30]1>C1COCC1>[Cl:9][C:10]1[C:15]([F:16])=[C:14]([CH:17]([CH3:18])[C:27]([C:21]2[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:20]=2[F:19])([OH:34])[CH2:28][N:29]2[CH:33]=[N:32][CH:31]=[N:30]2)[N:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 5880801-(2,4-Difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanoneHCID 2724682Lithium diisopropylamideHCID 167434454-Chloro-6-ethyl-5-fluoropyrimidine

Product 1

HCID 110363926-Chloro-alpha-(2,4-difluorophenyl)-5-fluoro-beta-methyl-alpha-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

To a solution of LDA (20 mmol) in THF1) (50 ml) (prepared by a similar method to that used in Example 1) under a nitrogen atmosphere and at -70° C. was added dropwise a solution of the product of part (ii) (3.2 g, 20 mmol) in THF1 (30 ml) over 15 minutes. The resulting mixture was stirred at this temperature for 3 hours. To the resulting solution was added a solution 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (4.46 g, 20 mmol) in THF (50 ml) and the mixture was maintained at -70° C. for 1 hour and then at -50° C. for a further 1 hour. The reaction was quenched by the addition of a solution of glacial acetic acid (1.2 g) in water (10 ml) and the mixture was allowed to warm to room temperature. The organic phase was separated, the aqueous phase extracted with ethyl acetate (20 ml) and the combined organic layers were dried over magnesium sulphate and concentrated under reduced pressure. Column chromatography of the residue on silica using 3:2 ethyl acetate/diethyl ether as the eluant first gave, after combination and evaporation of appropriate fractions and trituration with diethyl ether, the title compound, enantiomeric pair B (0.94 g, 12%), m.p. 92° C. Found: C,49.93; H,3.57; N,18.17; C16H13ClF3N5O requires: C,50.06; H,3.39; N,18.25%.

Workup

  1. waitat -50° C. for a further 1 hour
  2. customThe reaction was quenched by the addition of a solution of glacial acetic acid (1.2 g) in water (10 ml)
  3. temperatureto warm to room temperature
  4. customThe organic phase was separated
  5. extractionthe aqueous phase extracted with ethyl acetate (20 ml)
  6. dry with materialthe combined organic layers were dried over magnesium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customColumn chromatography of the residue on silica using 3:2 ethyl acetate/diethyl ether as the eluant first gave
  9. customafter combination and evaporation of appropriate fractions and trituration with diethyl ether

Sources & evidence

ORD record
ord-704d6f21c3834cfc9da96b8ba1167bd6
Source dataset
uspto-grants-1994_01
Patent number
US05278175

Reaction notes

Loading…