Ethyl Acetate → trans-Tert-butyl 3-(((benzyloxy)carbonyl)amino)-4-hydroxypyrrolidine-1-carboxylate

HRID 338960Notes

Reaction equation

HRID 338960 reaction equation
[NH2:1][C@H:2]1[C@H:6]([OH:7])[CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.C([O-])([O-])=O.[Na+].[Na+].[CH:21]1[CH:26]=[CH:25][C:24]([CH2:27][O:28][C:29](Cl)=[O:30])=[CH:23][CH:22]=1.C(OCC)(=O)C>O1CCOCC1.O>[CH2:27]([O:28][C:29]([NH:1][C@H:2]1[C@H:6]([OH:7])[CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1)=[O:30])[C:24]1[CH:25]=[CH:26][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 11275699(3R,4R)-3-Amino-1-Boc-4-hydroxypyrrolidine

Product 1

HCID 57970124trans-Tert-butyl 3-(((benzyloxy)carbonyl)amino)-4-hydroxypyrrolidine-1-carboxylateYield 67.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (3R,4R)-tert-butyl 3-amino-4-hydroxypyrrolidine-1-carboxylate (4.40 g, 21.76 mmol) and Na2CO3 (2.77 g, 26.11 mmol) in dioxane (50 mL) and water (50 mL) was added Cbz-Cl (3.87 mL, 26.11 mmol) at 0° C. The reaction mixture was warmed to ambient temperature and stirred at ambient temperature for 3 hours. Ethyl acetate (50 mL) was added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate) to give (3R,4R)-tert-butyl 3-(benzyloxycarbonylamino)-4-hydroxypyrrolidine-1-carboxylate (4.91 g, 67.1%) as an oil.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-95344e44caf246cda2a2c633c2fadfdb
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

Loading…