反応 #10418

反応方程式

7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester

chlorosulfonyl isocyanate

triethylamine

→

title compound

収率 15.9%

8,9-Difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diaza-phenalene-4,6-dione

収率 15.9%

溶媒

dichloromethane

反応条件

後処理

1. 1
   その他the solvent removed in vacuo
2. 2
   workup.ADDITIONThe residue is treated with a saturated sodium bicarbonate solution
3. 3
   抽出extracted with dichloromethane
4. 4
   乾燥The organic layer is dried (MgSO4)
5. 5
   ろ過filtered
6. 6
   濃縮concentrated in vacuo
7. 7
   workup.DISSOLUTIONThe residue is dissolved in 50 mL of tetrahydrofuran
8. 8
   温度After heating
9. 9
   温度at reflux for 4 hours
10. 10
    その他the solvent is removed in vacuo
11. 11
    その他the residue is triturated with 5 mL of dichloromethane/ethyl acetate (80:20)
12. 12
    その他The insoluble material is removed by filtration
13. 13
    洗浄washed with the above solvent mixture (2 mL)

実験手順

A solution of 1.5 g (6.2 mmol) of 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester (Example 32a) in 25 mL of dichloromethane is cooled to −20° C. and treated dropwise with 0.92 g (6.5 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at room temperature for 18 hours and the solvent removed in vacuo. The residue is treated with a saturated sodium bicarbonate solution and extracted with dichloromethane. The organic layer is dried (MgSO4), filtered, and concentrated in vacuo. The residue is dissolved in 50 mL of tetrahydrofuran, and the resulting solution is treated with 5.0 g (5.0 mmol) of triethylamine. After heating at reflux for 4 hours, the solvent is removed in vacuo, and the residue is triturated with 5 mL of dichloromethane/ethyl acetate (80:20). The insoluble material is removed by filtration, washed with the above solvent mixture (2 mL) to give 0.25 g of the title compound, mp 259–261° C. The filtrate is chromatographed over flash grade silica gel (230–400 mesh) eluting with dichloromethane/ethyl acetate (80:20) to give 0.38 g of starting material. Continued elution afforded an additional 0.2 g of the title compound. 1H NMR (400 MHz, CDCl3): 11.78 (s, 1H), 7.50 (m, 1H), 4.68 (m, 1H), 4.52 (d, 1H), 4.17 (d, 1H), 1.23 (d, 3H).

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