تفاعل #10418

معادلة التفاعل

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

chlorosulfonyl isocyanate

triethylamine

→

title compound

المردود 15.9%

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

المردود 15.9%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solvent removed in vacuo
2. 2
   workup.ADDITIONThe residue is treated with a saturated sodium bicarbonate solution
3. 3
   استخلاصextracted with dichloromethane
4. 4
   تجفيفThe organic layer is dried (MgSO4)
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated in vacuo
7. 7
   workup.DISSOLUTIONThe residue is dissolved in 50 mL of tetrahydrofuran
8. 8
   درجة الحرارةAfter heating
9. 9
   درجة الحرارةat reflux for 4 hours
10. 10
    أخرىthe solvent is removed in vacuo
11. 11
    أخرىthe residue is triturated with 5 mL of dichloromethane/ethyl acetate (80:20)
12. 12
    أخرىThe insoluble material is removed by filtration
13. 13
    غسيلwashed with the above solvent mixture (2 mL)

الإجراء التجريبي

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).

المصدر