Hydrazine → tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate

HRID 338845ノート

反応式

HRID 338845 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([N:13]2[CH2:17][CH2:16][C@H:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14]2)[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[NH2:26][NH2:27]>C(O)C(C)C>[F:10][C:9]([F:12])([F:11])[C@H:8]([N:13]1[CH2:17][CH2:16][C@H:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14]1)[C:5]1[CH:6]=[N:7][C:2]([NH:26][NH2:27])=[CH:3][CH:4]=1

参加物

4

反応物 2

HCID 9321HydrazineHCID 86707413tert-butyl (S)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate

生成物 1

HCID 86707414tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate収率 100.6%

試薬・触媒・溶媒 1

HCID 6560Isobutanol溶媒

実験手順

A solution of tert-butyl (S)-1-((R)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (68.5 g, 180.4 mmol) and anhydrous hydrazine (56.61 mL, 1804 mmol) in i-BuOH (80 mL) was stirred at 106° C. in a sealed flask for 16 hours. After cooling to ambient temperature, the solvent was removed under reduced pressure. The residue was partitioned in ethyl acetate (800 mL) and water (100 mL). The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (68.1 g, 95.6%) as white foam solid. Enantiomeric excess was determined by chiral HPLC (Chiralcel OD-H, 90% hexane/10% (1:1 MeOH/EtOH) at 1.0 mL/min, >99% d.e. (R,S)-diastereomer).

後処理

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned in ethyl acetate (800 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-18487635e55440b4aa01771103956739
出典データセット
uspto-grants-2014_11
特許番号
US08889704B2

反応ノート

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