Hydrochloric Acid → HCID 58042516、化合物

HRID 512060ノート

反応式

HRID 512060 の反応式
[H-].[Na+].[F:3][C:4]1([F:10])[CH2:7][CH:6]([CH2:8][OH:9])[CH2:5]1.Cl[C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][N:13]=1.Cl>C1COCC1>[Cl:18][C:17]1[C:12]([O:9][CH2:8][CH:6]2[CH2:7][C:4]([F:10])([F:3])[CH2:5]2)=[N:13][CH:14]=[CH:15][CH:16]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 169882,3-DichloropyridineHCID 24758Sodium hydrideHCID 45480377(3,3-Difluorocyclobutyl)methanol

生成物 1

HCID 58042516HCID 58042516、化合物収率 93.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

Sodium hydride (60% dispersion in mineral oil, 1.017 g, 70.6 mmol) was suspended in THF (30.0 mL) and the reaction was cooled to 0° C. under nitrogen with an ice bath. (3,3-Difluorocyclobutyl)methanol (Preparation 36, 2.95 g, 24.2 mmol) in THF (30 mL) was added dropwise to the mixture maintaining the temperature at 0° C. After stirring for 30 minutes, 2,3-dichloropyridine (3.25 g, 22.0 mmol) was added and the suspension was heated to reflux for 16 hours. An aqueous solution of HCl (1 M, 20 mL) was added and the reaction was extracted with EtOAc (2×100 mL). The combined organics were then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Biotage®, gradient of 0-50% EtOAc in heptane,) to afford the title compound (4.82 g, 85%).

後処理

  1. temperaturemaintaining the temperature at 0° C
  2. temperaturethe suspension was heated
  3. temperatureto reflux for 16 hours
  4. extractionthe reaction was extracted with EtOAc (2×100 mL)
  5. dry with materialThe combined organics were then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (Biotage®, gradient of 0-50% EtOAc in heptane,)

出典と根拠

ORDレコード
ord-c17f46f2df9e41c4aa91f2d0e8bc521f
出典データセット
uspto-grants-2015_08
特許番号
US09102621B2

反応ノート

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