반응 #2201606

반응 방정식

(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid

Ethyl 4′-[(1R)-1-(methylamino)-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylate

triethylamine

BOP

→

title compound

수율 75.0%

Ethyl 4′-[(1R)-1-[[(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetyl](methyl)amino]-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylate

수율 75.0%

용매

DMF

반응 조건

후처리

1. 1
   온도The reaction mixture was maintained at room temperature overnight
2. 2
   여과The reaction mixture was filtered
3. 3
   workup.ADDITIONThe filtrate was slowly added to 2500 mL of H2O with vigorous stirring
4. 4
   여과The resulting precipitate was collected by filtration
5. 5
   기타partitioned between 300 mL of brine solution and 1000 mL of DCM
6. 6
   건조The organic layer was dried over MgSO4
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   기타The brown residue was purified by column chromatography (250 g silica gel 60, 230-400 mesh, 2% MeOH and 0.5% NEt3 in CH2Cl2 as eluent)

실험 절차

Ethyl 4′-[(1R)-1-(methylamino)-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylate (crude, 26.5 g) was dissolved in 500 mL of DMF at room temperature with magnetic stirring. The resulting solution was treated with (6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid (28.8 g, 80.4 mmol, with 23 wt % LiCl) and cooled to 0° C. To this solution was added triethylamine (20.5 mL, 147.4 mmol) and BOP (35.5 g, 80.4 mmol). The reaction mixture was maintained at room temperature overnight. The reaction mixture was filtered. The filtrate was slowly added to 2500 mL of H2O with vigorous stirring. The resulting precipitate was collected by filtration and partitioned between 300 mL of brine solution and 1000 mL of DCM. The organic layer was dried over MgSO4, filtered, and concentrated. The brown residue was purified by column chromatography (250 g silica gel 60, 230-400 mesh, 2% MeOH and 0.5% NEt3 in CH2Cl2 as eluent) to give the title compound as a brown solid (31.3 g, 75% yield). MS (ES) m/e 626 [M+H]+.

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