Benzyl chloroformate → 3-Benzyloxycarbonylamino-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 519152Notes

Reaction equation

HRID 519152 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([NH2:14])([CH3:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[C:21](Cl)(=[O:30])[O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([NH:14][C:21]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:30])([CH3:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 57415917tert-Butyl 3-amino-3-methylpyrrolidine-1-carboxylate

Product 1

HCID 867275453-Benzyloxycarbonylamino-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-amino-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (5.0 g, 25 mmol) and potassium carbonate (3.8 g, 27 mmol) in THF (25 mL) and water (25 mL) was added benzyl carbonochloridate (4.6 g, 27 mmol) at 0° C. and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with water (25 mL) and extracted with EtOAc (3×15 mL). The combined organic phase was washed with brine (25 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 4% EtOAc in petroleum) to give 3-benzyloxycarbonylamino-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (5.5 g, 70%). 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 5H), 5.14-5.02 (m, 2H), 4.88-4.79 (m, 1H), 3.63-3.23 (m, 4H), 2.25 (m, 1H), 1.88-1.77 (m, 1H), 1.45 (s, 12H).

Workup

  1. extractionextracted with EtOAc (3×15 mL)
  2. washThe combined organic phase was washed with brine (25 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography on silica gel (eluting with 4% EtOAc in petroleum)

Sources & evidence

ORD record
ord-ffc621434a674da790075c08485a921a
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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