Sodium hydride → 3-[5-Fluoro-3-(tetrahydro-pyran-4-YL)-pyridin-2-yloxy]-cyclobutanecarboxylic acid methyl ester

HRID 1846787ノート

反応式

HRID 1846787 の反応式
[OH:1][CH:2]1[CH2:5][CH:4]([C:6]([O:8][CH3:9])=[O:7])[CH2:3]1.[H-].[Na+].F[C:13]1[C:18]([CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:17][C:16]([F:25])=[CH:15][N:14]=1>CN(C=O)C>[CH3:9][O:8][C:6]([CH:4]1[CH2:5][CH:2]([O:1][C:13]2[C:18]([CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[CH:17][C:16]([F:25])=[CH:15][N:14]=2)[CH2:3]1)=[O:7]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 12815112Cyclobutanecarboxylic acid, 3-hydroxy-, methyl esterHCID 585485232,5-Difluoro-3-(tetrahydro-pyran-4-YL)-pyridine

生成物 1

HCID 585486433-[5-Fluoro-3-(tetrahydro-pyran-4-YL)-pyridin-2-yloxy]-cyclobutanecarboxylic acid methyl ester収率 114.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a solution of methyl 3-hydroxycyclobutanecarboxylate (1.2 g, 9.0 mmol) in DMF (20 mL) was added sodium hydride (60% wt in mineral oil) (1.8 g, 45 mmol) at RT. The mixture was stirred for 1 h and then 2,5-difluoro-3-(tetrahydro-pyran-4-yl)-pyridine (1.8 g, 9.0 mmol) was added. The reaction mixture was heated to 60° C. for 3 h and then quenched with saturated NH4Cl. The solution was diluted with EtOAc and water and extracted with EtOAc (2×10 mL). The organic extracts were combined, washed with brine (10 mL), dried over MgSO4, filtered, and concentrated to get a residue, which was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) to give the product (3.2 g) as yellow oil.

後処理

  1. customquenched with saturated NH4Cl
  2. additionThe solution was diluted with EtOAc and water
  3. extractionextracted with EtOAc (2×10 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto get a residue, which
  9. customwas purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-bd943488edc349adada2d4b197862f21
出典データセット
uspto-grants-2015_02
特許番号
US08952037B2

反応ノート

読み込み中…