Réaction #76154

Équation de réaction

4

2,4-Dichloro-alpha(ethoxymethylene)-5-fluoro-beta-oxo-benzene propanoic acid ethyl ester

cyclopropylamine

→

7-Chloro-6-fluoro-1-cyclopropyl-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid

Solvants

methylene chloride

Conditions de réaction

Traitement

1. 1
   Températurewith cooling below 10° C
2. 2
   Autreevaporated to a dry mixture
3. 3
   workup.ADDITIONTo the dry mixture in dimethoxyethane (800 mL), a 60% sodium hydride-in-oil suspension (12.0 g) was added slowly
4. 4
   Températurewith cooling
5. 5
   workup.STIRRINGstirring
6. 6
   TempératureThe mixture was heated at 80-85° C. for 3 h under nitrogen atmosphere
7. 7
   TempératureIt was cooled
8. 8
   workup.ADDITIONwater (5 L) was added
9. 9
   Filtrationthe precipitate was filtered
10. 10
    Lavagewashed with water
11. 11
    Autredried
12. 12
    workup.ADDITIONA solution of sodium hydroxide (20.0 g) in water (500 mL) was added
13. 13
    Températurethe mixture was refluxed for 2 h
14. 14
    TempératureIt was cooled
15. 15
    Filtrationthe precipitate was filtered
16. 16
    LavageThe solid was washed with water and acetone

Mode opératoire

To a solution of 4 (80 g) in methylene chloride (800 mL), cyclopropylamine (44.0 g) was added with cooling below 10° C. The mixture was stirred at room temperature for 1 h and evaporated to a dry mixture. To the dry mixture in dimethoxyethane (800 mL), a 60% sodium hydride-in-oil suspension (12.0 g) was added slowly with cooling and stirring. The mixture was heated at 80-85° C. for 3 h under nitrogen atmosphere. It was cooled and water (5 L) was added and the precipitate was filtered and washed with water and dried. The ester was suspended in tetrahydrofuran (800 mL). A solution of sodium hydroxide (20.0 g) in water (500 mL) was added and the mixture was refluxed for 2 h. It was cooled and acidified with acetic acid and the precipitate was filtered. The solid was washed with water and acetone. wt=19.0 g of (7). m.p.=235-240° C.

Source