2,2,2-Trifluoro-1-methoxyethanol → 6-difluoromethyl-3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one

HRID 913026

反応式

HRID 913026 の反応式
[F:1][CH:2]([F:12])[C:3]1[N:4]([CH3:11])[CH:5]=[C:6]([OH:10])[C:7](=[O:9])[CH:8]=1.[C:13]([CH:17](OC)[OH:18])([F:16])([F:15])[F:14].C(=O)([O-])[O-].[K+].[K+]>>[F:12][CH:2]([F:1])[C:3]1[N:4]([CH3:11])[C:5]([CH:17]([OH:18])[C:13]([F:16])([F:15])[F:14])=[C:6]([OH:10])[C:7](=[O:9])[CH:8]=1

参加物

4

反応物 3

HCID 98922,2,2-Trifluoro-1-methoxyethanolHCID 11430Potassium CarbonateHCID 250189082-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-one

生成物 1

HCID 250186556-difluoromethyl-3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one収率 4.5%

反応条件

温度
100 °C

実験手順

A suspension of 2-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-one (0.50 g, 2.85 mmol), CF3CH(OH)OCH3 (2.37 g, 18.2 mmol) and potassium carbonate (0.122 g, 0.88 mmol) in a sealed parallel reactor test tube was heated to about 100° C. The progress of the reaction was monitored by HPLC Method 1 (Example 24), and only one major product peak was detected (HPLC peak percent area was about 20% after 1.5 h, and 38% after 3 h). The reaction mixture was heated for another 21 h, then cooled down to RT, and some white solid separated. The solid was collected by suction filtration. HPLC analysis of the solid dissolved in methanol showed the presence of 2-difluoromethyl-5-hydroxy-1-methyl-1H-pyridin-4-one and 6-difluoromethyl-3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one in 18/82 ratio. A portion of the solid was purified by column chromatography on silica gel (conc. NH4OH/isopropanol 10/100 v/v as eluant) to afford 6-difluoromethyl-3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (35 mg). HPLC Method 1 (Example 24), RT=11.3 min, HPLC purity (peak percent area): 97.9% at λ=280 nm. 1H NMR (DMSO-d6+1 drop of D2O) δ ppm: 7.12 (t, J=52.8 Hz, 1H), 6.56 (s, 1H), 5.83 (b, 1H), 3.79 (s, 3H). 19F NMR (DMSO-d6+1 drop of D2O) δ ppm: −73.3 (3F), −117.8 (2F). MS-ESI (m/z) 274.1 [M+1]+, 256.1, 228.1, 208.1 (100%), 180.1.

後処理

  1. custom(HPLC peak percent area was about 20% after 1.5 h, and 38% after 3 h)
  2. temperatureThe reaction mixture was heated for another 21 h
  3. temperaturecooled down to RT
  4. customsome white solid separated
  5. filtrationThe solid was collected by suction filtration
  6. dissolutionHPLC analysis of the solid dissolved in methanol
  7. customA portion of the solid was purified by column chromatography on silica gel (conc. NH4OH/isopropanol 10/100 v/v as eluant)

出典と根拠

ORDレコード
ord-b5d419c31068426ba1d2d8bfd7a3f0f1
出典データセット
uspto-grants-2011_09
特許番号
US08026261B2

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