Isopropyl Acetate → (S)-Tetrahydrofuran-3-yl (3-((phenoxycarbonyl)amino)benzyl)carbamate

HRID 1984967노트

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HRID 1984967 반응식
[N+:1]([C:4]1[CH:5]=[C:6]([CH:17]=[CH:18][CH:19]=1)[CH2:7][NH:8][C:9](=[O:16])[O:10][C@H:11]1[CH2:15][CH2:14][O:13][CH2:12]1)([O-])=O.C(OC(C)C)(=O)C.[H][H].S([O-])([O-])(=O)=O.[Na+].[Na+].Cl[C:37]([O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:38]>O.[Pd]>[C:40]1([O:39][C:37](=[O:38])[NH:1][C:4]2[CH:19]=[CH:18][CH:17]=[C:6]([CH2:7][NH:8][C:9]([O:10][C@H:11]3[CH2:15][CH2:14][O:13][CH2:12]3)=[O:16])[CH:5]=2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

참가 물질

8

반응물 5

HCID 7915Isopropyl AcetateHCID 15891Phenyl chloroformateHCID 24436Sodium SulfateHCID 57718888(S)-Tetrahydrofuran-3-yl (3-nitrobenzyl)carbamateHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 17748134(S)-Tetrahydrofuran-3-yl (3-((phenoxycarbonyl)amino)benzyl)carbamate수율 91%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 962Water용매

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온도
60 °C

실험 절차

A mixture of 2c (50 g, 1.00 equivalent), 5% Pd/C (0.75 g, 50% water, 0.75 wt %) and isopropyl acetate (400 ml, 8 volumes) was added to a hydrogenation vessel under nitrogen and heated to 60° C. The vessel was pressurized with hydrogen (1.00 bar overpressure) and the mixture stirred at 60° C. The reaction was complete within 3 hours. The pressure was released and the vessel purged with nitrogen. The mixture was filtered through a pad of Celite® and then the hydrogenation vessel and pad were rinsed with isopropyl acetate (100 ml, 2 volumes). The solution of 2d in isopropyl acetate was then combined with a solution of sodium sulfate (29.3 g, 1.10 equivalents) in water (150 ml, 3 vol) and then the mixture was heated to 70° C. Phenyl chloroformate (25.7 ml, 1.10 equivalents) was then added to the mixture while maintaining a temp. of 70° C. The reaction was stirred for 30 min after the end of addition and then the stirring was stopped. The phases were allowed to separate and the aqueous phase was removed. Water (150 ml, 3 vol) was then added and the mixture stirred for an additional 30 min before the stirring was stopped. The phases were allowed to separate and the aqueous phase removed. The mixture was then distilled at atmospheric pressure to azeotropically remove water from the organic phase. Compound 2e precipitated from solution when all of the water was removed. Distillation continued until there were 4 volumes of solvent remaining. The mixture was cooled to 20° C. over 5 hours then filtered to isolate the solid. The reactor and filter cake were washed with isopropyl acetate (2 vol) then the cake was dried under vacuum at 50° C. to afford 61.1 g (91%) of 2e.

후처리

  1. additionwas added to a hydrogenation vessel under nitrogen
  2. customthe vessel purged with nitrogen
  3. filtrationThe mixture was filtered through a pad of Celite®
  4. washthe hydrogenation vessel and pad were rinsed with isopropyl acetate (100 ml, 2 volumes)
  5. temperaturethe mixture was heated to 70° C
  6. temperaturewhile maintaining a temp
  7. customof 70° C
  8. stirringThe reaction was stirred for 30 min
  9. additionafter the end of addition
  10. customto separate
  11. customthe aqueous phase was removed
  12. additionWater (150 ml, 3 vol) was then added
  13. stirringthe mixture stirred for an additional 30 min before the stirring
  14. customto separate
  15. customthe aqueous phase removed
  16. distillationThe mixture was then distilled at atmospheric pressure to azeotropically remove water from the organic phase
  17. customCompound 2e precipitated from solution when all of the water
  18. customwas removed
  19. distillationDistillation
  20. temperatureThe mixture was cooled to 20° C. over 5 hours
  21. filtrationthen filtered
  22. customto isolate the solid
  23. filtrationThe reactor and filter cake
  24. washwere washed with isopropyl acetate (2 vol)
  25. customthe cake was dried under vacuum at 50° C.

출처 및 근거

ORD 기록
ord-34cb3ea6695f4b1fb34ca68accb5cc77
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07544810B2

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