Sodium hydride → (S)-3-[(S)-2-Azido-1-(4-trifluoromethylphenoxy)ethyl]pyrrolidine-1-carboxylic acid t-butyl ester

HRID 1889140Notes

Reaction equation

HRID 1889140 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@H:13]([OH:18])[CH2:14][N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@H:13]([O:18][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH2:14][N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67873Benzene, 1-fluoro-4-(trifluoromethyl)-HCID 86666088(S)-3-((S)-2-azido-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester

Product 1

HCID 86666089(S)-3-[(S)-2-Azido-1-(4-trifluoromethylphenoxy)ethyl]pyrrolidine-1-carboxylic acid t-butyl esterYield 69.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-3-((S)-2-Azido-1-hydroxyethyl)pyrrolidine-1-carboxylic acid t-butyl ester (1.3 g, 5.0 mmol, 1.0 eq.) was combined with DMF (18 mL). Washed and dried NaH (362 mg, 15.1 mmol, 3.0 eq.) was carefully added in 3 separate portions. The resulting mixture was stirred at room temperature for 15 minutes under nitrogen. 4-Fluorobenzotrifluoride (1.9 mL, 15.1 mmol, 3.0 eq.) was added and the mixture was stirred at 100° C. for 3 hours. The mixture was then concentrated under reduced pressure. The resulting material was dissolved in EtOAc (15 mL) and washed with water (1×15 mL). The organic layer was concentrated and purified by flash chromatography (0-100% EtOAc/hexanes) to yield (S)-3-[(S)-2-azido-1-(4-trifluoromethylphenoxy)ethyl]-pyrrolidine-1-carboxylic acid t-butyl ester (1.4 g).

Workup

  1. washWashed
  2. customseparate portions
  3. stirringthe mixture was stirred at 100° C. for 3 hours
  4. concentrationThe mixture was then concentrated under reduced pressure
  5. dissolutionThe resulting material was dissolved in EtOAc (15 mL)
  6. washwashed with water (1×15 mL)
  7. concentrationThe organic layer was concentrated
  8. custompurified by flash chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e65b14823fad459f8ff4f4429f1086f5
Source dataset
uspto-grants-2013_08
Patent number
US08501964B2

Reaction notes

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