Sodium hydride → (S)-benzyl 3-(tert-butoxycarbonyl(3-fluoropropyl)amino)pyrrolidine-1-carboxylate

HRID 60308Notes

Reaction equation

HRID 60308 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)S(O[CH2:30][CH2:31][CH2:32][F:33])(=O)=O.[H-].[Na+]>O1CCCC1.O.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]([CH2:30][CH2:31][CH2:32][F:33])[C@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 14555479Benzyl (3S)-3-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylateHCID 447173943-Fluoropropyl trifluoromethanesulfonate

Product 1

HCID 58365182(S)-benzyl 3-(tert-butoxycarbonyl(3-fluoropropyl)amino)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (S)-benzyl 3-(tert-butoxycarbonylamino)pyrrolidine-1-carboxylate (400 mg, 1.2 mmol) and 3-fluoropropyl trifluoromethanesulfonate (433 mg, 2.1 mmol) in tetrahydrofuran (10 mL) was added sodium hydride as 60% dispersion in mineral oil (146 mg, 3.6 mmol). The reaction mixture was stirred at ambient temperature for 30 minutes and then diluted with water (20 mL) and methylene chloride (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified flash chromatography (silica, 40 g, ISCO, 1-20% methanol in methylene chloride) to afford the title compound as a colorless oil, which was used in the next step without any further purification (475 mg, 100%).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified flash chromatography (silica, 40 g, ISCO, 1-20% methanol in methylene chloride)

Sources & evidence

ORD record
ord-01a09ae1556744ecbf99bf55f6e7808e
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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