Sulfuric Acid → HCID 21939656、化合物

HRID 2390949ノート

反応式

HRID 2390949 の反応式
C(OC([N:8]([C:28]1[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=1[F:35])[C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15]CC)=[O:14])=[C:11]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[N:10]=1)=O)(C)(C)C.S(=O)(=O)(O)O>>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C:11]1[N:10]=[C:9]([NH:8][C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:29]=2[F:35])[CH:19]=[CH:18][C:12]=1[C:13]([OH:15])=[O:14]

参加物

3

反応物 2

HCID 1118Sulfuric Acid2 回HCID 21062880Ethyl 6-(tert-butoxycarbonyl(2,6-difluorophenyl)amino)-2-(2,4-difluorophenyl)nicotinate

生成物 1

HCID 21939656HCID 21939656、化合物

反応条件

温度
100 °C

実験手順

To Compound 8 (100 g, 0.204 mol, 1.00 eq) was added a 7M sulfuric acid solution prepared by the slow addition of concentrated sulfuric acid (285 mL, 2.85 vol, 5.24 mol) to distilled water (465 mL, 4.65 vol) while keeping the temperature below 50° C. The mixture was heated at 100±5° C. until the reaction was complete. The mixture was then cooled to 30±5° C. and additional water (750 mL, 7.5 vol) was added. Isopropyl acetate (2 L, 20 vol) was then added and the mixture was stirred for 15 minutes. Stirring was stopped and the phases were allowed to separate. The aqueous phase was separated and water (7.5 vol) was charged to the organic phase. The mixture was stirred for 15 minutes, polish filtered, then the aqueous phase was drained. The total volume of the organic layer was reduced to 4 vol by vacuum distillation at 45±5° C. The resulting slurry was cooled to −10° C. for 12 hours and filtered. The filter and cake was washed with cold isopropyl acetate (3 vol) and the solids were dried under vacuum at 50±5° C. to give the title Compound, 9, as a white solid. (1H NMR, 500 MHz; DMSO-d6) δ 12.50 (s, 1H), 9.25 (s, 1H), 8.07 (d, 1H), 7.39 (q, 1H), 7.29 (m, 1H), 7.18 (m, 3H), 7.09 (m, 1H), 6.25 (m, 1H).

後処理

  1. distillationto distilled water (465 mL, 4.65 vol)
  2. customthe temperature below 50° C
  3. temperatureThe mixture was then cooled to 30±5° C.
  4. additionadditional water (750 mL, 7.5 vol) was added
  5. additionIsopropyl acetate (2 L, 20 vol) was then added
  6. stirringStirring
  7. customto separate
  8. customThe aqueous phase was separated
  9. additionwater (7.5 vol) was charged to the organic phase
  10. stirringThe mixture was stirred for 15 minutes
  11. filtrationpolish filtered
  12. distillationThe total volume of the organic layer was reduced to 4 vol by vacuum distillation at 45±5° C
  13. temperatureThe resulting slurry was cooled to −10° C. for 12 hours
  14. filtrationfiltered
  15. filtrationThe filter
  16. washcake was washed with cold isopropyl acetate (3 vol)
  17. customthe solids were dried under vacuum at 50±5° C.

出典と根拠

ORDレコード
ord-83a5726cfe5d479c829c73c0c1afe757
出典データセット
uspto-grants-2012_09
特許番号
US08273896B2

反応ノート

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