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

HRID 10322

反応式

HRID 10322 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

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).

後処理

  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)

出典と根拠

ORDレコード
ord-9609d165691a467a99ceed9a09f8958b
出典データセット
uspto-grants-2006_08
特許番号
US07094780B1

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