Sulfuric Acid → HCID 21939656, 화합물

HRID 1257094노트

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HRID 1257094 반응식
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]

참가 물질

3

반응물 2

HCID 1118Sulfuric Acid2회HCID 21062880Ethyl 6-(tert-butoxycarbonyl(2,6-difluorophenyl)amino)-2-(2,4-difluorophenyl)nicotinate

생성물 1

HCID 21939656HCID 21939656, 화합물

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온도
100 °C

실험 절차

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).

후처리

  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.

출처 및 근거

ORD 기록
ord-4b91888182404b5bbe834707d65ec185
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461345B2

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