Lithium Hydroxide → 2-(Benzo[1,3]dioxol-5-yloxy)-5-fluoro-nicotinic acid

HRID 1297584ノート

反応式

HRID 1297584 の反応式
Cl[C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.C(OC(=O)C1C=C(F)C=NC=1Cl)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:35]1[O:39][C:38]2[CH:40]=[C:41]([OH:44])[CH:42]=[CH:43][C:37]=2[O:36]1.[OH-].[Li+]>O.O1CCOCC1.C(O)C>[O:36]1[C:37]2[CH:43]=[CH:42][C:41]([O:44][C:2]3[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=3[C:4]([OH:6])=[O:5])=[CH:40][C:38]=2[O:39][CH2:35]1

参加物

10

反応物 6

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 24386Thionyl ChlorideHCID 68289SesamolHCID 11390082Ethyl 2-chloro-5-fluoronicotinateHCID 114352432-Chloro-5-fluoronicotinic acid

生成物 1

HCID 220584122-(Benzo[1,3]dioxol-5-yloxy)-5-fluoro-nicotinic acid

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

2-Chloro-5-fluoro-nicotinic acid (synthesized in accordance with the procedures described in European patent: EP 0634413 A1) was converted to the corresponding ethyl ester with anhydrous ethanol and excess thionyl chloride, then worked up in the usual manner. To 2-chloro-5-fluoro-nicotinic acid ethyl ester (5.0 g) in an oven-dried 250 mL flask was added cesium carbonate (9.60 g), sesamol (4.07 g), and 50 mL of anhydrous dioxane. The reaction was stirred overnight at 100° C. Lithium hydroxide (2.94 g) in 10 mL water was added, and the reaction was again allowed to stir overnight at 100° C. The dioxane was then evaporated under a nitrogen stream. The residue was then taken up in 50 mL water, acidified with conc. hydrochloric acid to pH=3, and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The dried residue was washed with ethyl acetate (20 mL) and dried under high vacuum, giving the title compound (2.96 g).

後処理

  1. stirringto stir overnight at 100° C
  2. customThe dioxane was then evaporated under a nitrogen stream
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined organic extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washThe dried residue was washed with ethyl acetate (20 mL)
  8. customdried under high vacuum

出典と根拠

ORDレコード
ord-6ab889b354ec4937bb633fe3ea42afc5
出典データセット
uspto-grants-2007_07
特許番号
US07250518B2

反応ノート

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