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

HRID 1297584

반응식

HRID 1297584 반응식
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

참가 물질

10

반응물 6

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

생성물 1

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

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6ab889b354ec4937bb633fe3ea42afc5
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07250518B2

연결된 노트

불러오는 중…