Triethylamine → 8,9-Difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diaza-phenalene4,6-dione

HRID 10322

반응식

HRID 10322 반응식
CO[C:3]([C:5]1[CH:6]=[C:7]([F:17])[C:8]([F:16])=[C:9]2[O:14][CH2:13][CH:12]([CH3:15])[NH:11][C:10]=12)=[O:4].ClS([N:22]=[C:23]=[O:24])(=O)=O.C(N(CC)CC)C>ClCCl>[F:17][C:7]1[CH:6]=[C:5]2[C:10]3[N:11]([CH:12]([CH3:15])[CH2:13][O:14][C:9]=3[C:8]=1[F:16])[C:23](=[O:24])[NH:22][C:3]2=[O:4]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 210411927,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylic acid methyl ester

생성물 1

HCID 219791108,9-Difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diaza-phenalene4,6-dione수율 15.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  1. customthe solvent removed in vacuo
  2. additionThe residue is treated with a saturated sodium bicarbonate solution
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic layer is dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue is dissolved in 50 mL of tetrahydrofuran
  8. temperatureAfter heating
  9. temperatureat reflux for 4 hours
  10. customthe solvent is removed in vacuo
  11. customthe residue is triturated with 5 mL of dichloromethane/ethyl acetate (80:20)
  12. customThe insoluble material is removed by filtration
  13. washwashed with the above solvent mixture (2 mL)

출처 및 근거

ORD 기록
ord-9609d165691a467a99ceed9a09f8958b
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094780B1

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