Sodium hydride → Methyl 5-chloro-6-[(1,3-difluoropropan-2-yl)oxy]nicotinate

HRID 217468

反応式

HRID 217468 の反応式
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[H-].[Na+].[F:15][CH2:16][CH:17]([OH:20])[CH2:18][F:19]>C1COCC1>[Cl:1][C:2]1[C:3]([O:20][CH:17]([CH2:18][F:19])[CH2:16][F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 679851,3-Difluoro-2-propanolHCID 2782166Methyl 5,6-Dichloronicotinate

生成物 1

HCID 67363966Methyl 5-chloro-6-[(1,3-difluoropropan-2-yl)oxy]nicotinate収率 80.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

Methyl 5,6-dichloronicotinate (1.5 g) and 60% sodium hydride (640 mg) were dissolved in THF (45 mL). 1,3-Difluoropropan-2-ol (1.5 g) was added thereto at 0° C., followed by stirring at 0° C. for 3 hours, and the reaction solution was quenched with aqueous NH4Cl. After extraction with EtOAc, the organic layer was dried over MgSO4 and then filtered, and the desiccant was removed. The vehicle was evaporated under reduced pressure, followed by purification by silica gel column chromatography (hexane:AcOEt=100:0 to 50:50) to obtain methyl 5-chloro-6-[(1,3-difluoropropan-2-yl)oxy]nicotinate (1.56 g) as a colorless liquid.

後処理

  1. customat 0° C.
  2. customthe reaction solution was quenched with aqueous NH4Cl
  3. extractionAfter extraction with EtOAc
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customthe desiccant was removed
  7. customThe vehicle was evaporated under reduced pressure
  8. customfollowed by purification by silica gel column chromatography (hexane:AcOEt=100:0 to 50:50)

出典と根拠

ORDレコード
ord-6d3346eb5732435ab3e1c1b3e3aff310
出典データセット
uspto-grants-2012_06
特許番号
US08193378B2

関連ノート

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