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 865807ノート

反応式

HRID 865807 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-70 °C

実験手順

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 of 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: C50.06; H,3.39; N,18.25%.

後処理

  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

出典と根拠

ORDレコード
ord-007f7bd9cc7d40b7bb42265fc239bf10
出典データセット
uspto-grants-1996_10
特許番号
US05567817

反応ノート

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