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Trifluoroacetic acid → (2R,5R)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine

HRID 243659
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HRID 243659 반응식
[Si:1]([O:8][C@H:9]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:10]([NH:25]C(=O)OCC1C=CC(OC)=CC=1)[CH2:11][CH2:12][C:13](=O)[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C([BH3-])#N.[Na+]>C(Cl)Cl>[Si:1]([O:8][C@H:9]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:10]1[CH2:11][CH2:12][C@@H:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[NH:25]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2].[Si:1]([O:8][C@H:9]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:10]1[CH2:11][CH2:12][C@H:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[NH:25]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 579074284-methoxybenzyl [(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)-4-oxopentyl]carbamate

생성물 2

HCID 57907554(2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine
HCID 57907644
(2R,5R)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine
수율 26%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of MOZ protected ketone amine (from Step G, 34 g, 56 mmol) in DCM (350 ml) was added TFA (256 ml) and the resulting mixture stirred at room temperature for 1.5 h. The solution was evaporated under vacuum and residue partitioned between DCM and sat. NaHCO3. The organic layer was dried over MgSO4, filtered and evaporated. The residue was dissolved in MeOH (750 ml) and cooled to 0° C. via ice/water bath. Sodium cyanoborohydride (21.2 g, 337 mmol) was then added and the resulting mixture was stirred overnight to allow to warm to room temperature. The mixture was quenched by addition of water and the organics removed under vacuum. The aqueous layer was then extracted with EtOAc (x2) and the combined EtOAc layers washed with sat. NaCl, dried over MgSO4, filtered and evaporated under vacuum. The residue was purified by column chromatography on silica (eluent: gradient rising from 100% Hexanes to 35% EtOAc in Hexanes) to give 16.4 g (63.4%) of the first isomer, (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine, and 3.1 g (12%) of the second isomer (2R,5R)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine.

후처리

  1. customThe solution was evaporated under vacuum and residue
  2. custompartitioned between DCM and sat. NaHCO3
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe residue was dissolved in MeOH (750 ml)
  7. temperaturecooled to 0° C. via ice/water bath
  8. stirringthe resulting mixture was stirred overnight
  9. temperatureto warm to room temperature
  10. customThe mixture was quenched by addition of water
  11. customthe organics removed under vacuum
  12. extractionThe aqueous layer was then extracted with EtOAc (x2)
  13. washthe combined EtOAc layers washed with sat. NaCl
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. customevaporated under vacuum
  17. customThe residue was purified by column chromatography on silica (eluent: gradient rising from 100% Hexanes to 35% EtOAc in Hexanes)

출처 및 근거

ORD 기록
ord-9d8f1280130748518d420b44dc2b9f3d
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08653260B2

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