Sodium hydride → HCID 86707440, compound

HRID 338898Notes

Reaction equation

HRID 338898 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].[H-].[Na+].CS(O[CH2:31][CH2:32][O:33][C:34]([CH3:37])([CH3:36])[CH3:35])(=O)=O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH2:31][CH2:32][O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[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

5

Reactant 3

HCID 24758Sodium hydrideHCID 14555479Benzyl (3S)-3-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylateHCID 184649242-[(2-Methylpropan-2-yl)oxy]ethyl methanesulfonate

Product 1

HCID 86707440HCID 86707440, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-benzyl 3-(tert-butoxycarbonylamino)pyrrolidine-1-carboxylate (2.50 g, 7.80 mmol) in anhydrous DMF (20 mL) cooled to 0° C. in an ice bath was added a 60% dispersion of sodium hydride in mineral oil (0.47 g, 11.7 mmol). The mixture was allowed to warm to ambient temperature and stirred for 1 hour. 2-tert-Butoxyethyl methanesulfonate (2.3 g, 11.7 mmol) was added and the mixture was stirred at 0° C. in an ice bath, then allowed to slowly warm to ambient temperature and stirred for 18 hours. The mixture was partitioned between water (50 mL) and ethyl acetate (100 mL). The layers were separated and washed with aqueous 1N HCl, water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage, 40M; 20% ethyl acetate/hexane) to afford (S)-benzyl 3-(tert-butoxycarbonyl(2-tert-butoxyethyl)amino)pyrrolidine-1-carboxylate (2.87 g, 88%).

Workup

  1. stirringthe mixture was stirred at 0° C. in an ice bath
  2. temperatureto slowly warm to ambient temperature
  3. stirringstirred for 18 hours
  4. customThe mixture was partitioned between water (50 mL) and ethyl acetate (100 mL)
  5. customThe layers were separated
  6. washwashed with aqueous 1N HCl, water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography (Biotage, 40M; 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-00d6589429e44f488ef098e0331f8a58
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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