반응 #325383

반응 방정식

2-amino-5-bromo-benzoic acid

methylamine

p-toluenesulfonic acid monohydrate

triethyl orthopropionate

→

6-Bromo-2-ethyl-3-methyl-3H-quinazolin-4-one

수율 39.9%

용매

methanol

반응 조건

후처리

1. 1
   온도The reaction was refluxed for 18 hours, at which time it
2. 2
   농축The solution was concentrated under reduced pressure
3. 3
   기타The residue was partitioned between sodium carbonate aqueous (50 ml) and dichloromethane (50 ml)
4. 4
   세척The organic layer was then washed with saturated brine (2×30 ml)
5. 5
   건조The combined organic phase was dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   기타The solvent was removed under vacuum
8. 8
   기타The resulting residue was purified by silica gel chromatography with 100% dichloromethane
9. 9
   기타The product was collected
10. 10
    기타was dried under reduced pressure

실험 절차

To a stirred solution of 2-amino-5-bromo-benzoic acid (10.00 g, 46.38 mmol) in methanol (25 mL) was added methylamine (100 ml of 2 M solution in methanol), p-toluenesulfonic acid monohydrate (8.82 g, 46.38 mmol), and triethyl orthopropionate (40.87 g, 231.9 mmol). The reaction was refluxed for 18 hours, at which time it was allowed to cool to room temperature. The solution was concentrated under reduced pressure. The residue was partitioned between sodium carbonate aqueous (50 ml) and dichloromethane (50 ml). The organic layer was then washed with saturated brine (2×30 ml). The combined organic phase was dried over magnesium sulfate and filtered. The solvent was removed under vacuum. The resulting residue was purified by silica gel chromatography with 100% dichloromethane. The product was collected and was dried under reduced pressure to give 6-Bromo-2-ethyl-3-methyl-3H-quinazolin-4-one (Yield 4.92 g, 39.9%). 1H NMR (400 MHz, CDCl3): □ 1.42 (t, 3H, J=7.33 Hz), 2.86 (dd, 2H, J=14.65, 7.58 Hz), 7.45 (d, 1H, J=8.5 Hz), 7.80 (dd, 1H, J=8.50, 2.02 Hz), 8.40 (d, 1H, J=2.05 Hz). MS m/z calc. 266.01, found (ESI); 267.0 (M+1)+. Retention time 2.44 minutes.

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