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

HRID 887092ノート

反応式

HRID 887092 の反応式
COC1C=CC(C[N:8]([C@@H:12]([C@H:27]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:13][CH2:14][C:15](=O)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)C(=O)[O-])=CC=1.C(O)(C(F)(F)F)=O.C([BH3-])#N.[Na+]>C(Cl)Cl>[Si:35]([O:34][C@H:27]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C@H:12]1[CH2:13][CH2:14][C@@H:15]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[NH:8]1)([C:38]([CH3:40])([CH3:41])[CH3:39])([CH3:36])[CH3:37].[Si:35]([O:34][C@H:27]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C@H:12]1[CH2:13][CH2:14][C@H:15]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[NH:8]1)([C:38]([CH3:40])([CH3:41])[CH3:39])([CH3:36])[CH3:37]

参加物

6

反応物 3

HCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 669398074-methoxybenzyl[(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)-4-oxopentyl]carbamate

生成物 2

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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 evaported. 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 (×2) 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.

後処理

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

出典と根拠

ORDレコード
ord-9b34f819221e43e5bff7d12307eb740f
出典データセット
uspto-grants-2012_08
特許番号
US08247415B2

反応ノート

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