반응 #446288

반응 방정식

4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine

2-(3-bromopropyl)-3-hydroxy-1-isoindolinone

oxalic acid

triethylamine

→

3-hydroxy-2-[3-(4-(4-fluorophenyl)-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate

수율 59.2%

용매

toluene

toluene

toluene

methyl ethyl ketone

methyl ethyl ketone

methylene chloride

반응 조건

후처리

1. 1
   기타close to 20° C. and in the course of 10 minutes
2. 2
   기타close to 111° C. for 3 hours
3. 3
   온도After cooling to a temperature
4. 4
   기타close to 20° C
5. 5
   기타the precipitate formed
6. 6
   기타is separated by filtration
7. 7
   세척washed with toluene (3×50 cc)
8. 8
   농축concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 60° C
9. 9
   기타The residue obtained
10. 10
    workup.ADDITIONthe solution poured onto silica (1 kg)
11. 11
    세척Elution
12. 12
    workup.ADDITIONis carried out with a mixture of methylene chloride and methanol (98-2 by volume)
13. 13
    농축the next 4000 cc are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
14. 14
    기타The oil obtained
15. 15
    온도agitation is maintained for about 1 hour
16. 16
    기타The precipitate formed
17. 17
    기타is separated by filtration
18. 18
    세척washed with methyl ethyl ketone (20 cc)
19. 19
    기타recrystallized from a boiling mixture of isopropanol and isopropyl ether (75-25 by volume,150 cc)

실험 절차

A solution of 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (12.3 g) in toluene (20 cc) is added to a solution of 2-(3-bromopropyl)-3-hydroxy-1-isoindolinone (18.9 g) in toluene (200 cc), at a temperature close to 20° C. and in the course of 10 minutes, followed by a solution of triethylamine (9.8 cc) in toluene (20 cc). The mixture is agitated at a temperature close to 111° C. for 3 hours. After cooling to a temperature close to 20° C, the precipitate formed is separated by filtration and washed with toluene (3×50 cc). The organic phases are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 60° C. The residue obtained is dissolved in methylene chloride (50 cc) and the solution poured onto silica (1 kg) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (98-2 by volume). The first 4000 cc are eliminated and the next 4000 cc are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The oil obtained is dissolved in methyl ethyl ketone (70 cc). A solution of oxalic acid (1.6 g) in methyl ethyl ketone (20 cc) is added, and agitation is maintained for about 1 hour. The precipitate formed is separated by filtration, washed with methyl ethyl ketone (20 cc), and then recrystallized from a boiling mixture of isopropanol and isopropyl ether (75-25 by volume,150 cc). 4.8 g of 3-hydroxy-2-[3-(4-(4-fluorophenyl)-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are obtained, melting at 93° C.

출처