반응 #1127702

반응 방정식

4-[(R)-1-(3,5-dichloro-4-fluoro-phenyl)-5-iodo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile

Acetic anhydride

sodium formate

Hunig's base

LiCl

→

title compound

수율 86.6%

(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid

수율 86.6%

용매

DMF

DMF

반응 조건

후처리

1. 1
   기타This was sealed with the screw
2. 2
   기타cap
3. 3
   기타The vessel was capped tightly
4. 4
   workup.STIRRINGto stir at 80° C. for 20 h
5. 5
   온도In a well ventilated fume hood, the reaction was cooled to room temperature
6. 6
   기타the screw cap
7. 7
   기타was slowly removed
8. 8
   기타The reaction was transferred to a seperatory funnel
9. 9
   workup.ADDITIONcontaining a solution of aqueous HCl (2N, 1 L)
10. 10
    기타The layers were separated
11. 11
    세척the organic phase was washed with aqueous 2N HCl (1 L)
12. 12
    추출The combined aqueous phase was extracted with EtOAc (2×1 L)
13. 13
    건조The combined organic phase was dried with MgSO4
14. 14
    농축concentrated in vacuo
15. 15
    workup.ADDITIONToluene was added to the dark colored residue
16. 16
    기타precipitation of a solid
17. 17
    여과The solid was filtered
18. 18
    세척washed with 1:1 toluene
19. 19
    농축The filtrate was concentrated and re-processed in a similar manner
20. 20
    기타to give additional solids

실험 절차

Acetic anhydride (14.0 mL, 148 mmol), sodium formate (15.1 g, 222 mmol) and Hunig's base (25.8 mL, 148 mmol) were suspended in anhydrous DMF (50 mL) in a 1000 mL screw-top glass pressure-vessel. This was sealed with the screw cap and allowed to stir for 45 min at room temperature. To this mixture was added a solution of 4-[(R)-1-(3,5-dichloro-4-fluoro-phenyl)-5-iodo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[1,2-a]imidazol-3-ylmethyl]-benzonitrile (40.0 g, 73.9 mmol) in anhydrous DMF (200 mL) followed by Pd(OAc)2 (830 mg, 3.70 mmol) and anhydrous LiCl (9.40 g, 221 mmol). The vessel was capped tightly and allowed to stir at 80° C. for 20 h. In a well ventilated fume hood, the reaction was cooled to room temperature and the screw cap was slowly removed allowing for gas release. The reaction was transferred to a seperatory funnel containing a solution of aqueous HCl (2N, 1 L) using EtOAc (1 L). The layers were separated and the organic phase was washed with aqueous 2N HCl (1 L). The combined aqueous phase was extracted with EtOAc (2×1 L). The combined organic phase was dried with MgSO4 and concentrated in vacuo. Toluene was added to the dark colored residue causing precipitation of a solid. The solid was filtered and washed with 1:1 toluene:hexanes followed by hexanes. The filtrate was concentrated and re-processed in a similar manner to give additional solids. A total of 29.4 g of the title compound was obtained as an off-white solid, m/z. 459.4 [M+H]+.

출처