반응 #366850

반응 방정식

1,1′-(azodicarbonyl)dipiperidine

4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline

3-benzyloxypropanol

tributylphosphine

→

7-(3-benzyloxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride

수율 56.6%

용매

ether

methylene chloride

반응 조건

후처리

1. 1
   workup.WAITfor 18 hours at ambient temperature
2. 2
   workup.STIRRINGstirred for 15 minutes
3. 3
   기타The insolubles were removed by filtration
4. 4
   기타the volatiles were removed from the filtrate by evaporation
5. 5
   기타The residue was partitioned between ethyl acetate and water
6. 6
   기타the organic layer was separated
7. 7
   건조dried (MgSO4)
8. 8
   기타the solvent removed by evaporation
9. 9
   workup.ADDITIONA 1M solution of ethereal hydrogen chloride was added to the residue
10. 10
    기타the resulting solution was reduced in volume by evaporation
11. 11
    여과the resulting precipitate was collected by filtration
12. 12
    기타dried

실험 절차

1,1′-(azodicarbonyl)dipiperidine (480 mg, 1.9 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.63 mmol), 3-benzyloxypropanol (150 μl, 0.95 mmol) and tributylphosphine (459 μl, 1.86 mmol) in methylene chloride (20 ml) at 5° C. The reaction was stirred for 1 hour at 5° C. and then for 18 hours at ambient temperature. The mixture was diluted with ether and stirred for 15 minutes. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was partitioned between ethyl acetate and water, and the organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. A 1M solution of ethereal hydrogen chloride was added to the residue, the resulting solution was reduced in volume by evaporation and the resulting precipitate was collected by filtration and dried to give 7-(3-benzyloxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (90 mg, 31%).

출처