Benzyl chloroformate → O1-benzyl O2-methyl 4-methylenepyrrolidine-1,2-dicarboxylate

HRID 2039183Notes

Reaction equation

HRID 2039183 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][CH:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])(C)C.Cl.O1CCOC[CH2:19]1.CCN(C(C)C)C(C)C.C(OC(Cl)=O)[C:34]1[CH:39]=[CH:38]C=[CH:36][CH:35]=1>CO.O>[CH3:19][O:16][C:14]([CH:9]1[CH2:10][C:11](=[CH2:13])[CH2:12][N:8]1[C:6]([O:5][CH2:1][C:4]1[CH:38]=[CH:39][CH:34]=[CH:35][CH:36]=1)=[O:7])=[O:15]

Participants

7

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 204431481,4-Dioxane hydrochlorideHCID 217625641-(tert-Butoxycarbonyl)-4-methylenepyrrolidine-2-carboxylic acid

Product 1

HCID 21922647O1-benzyl O2-methyl 4-methylenepyrrolidine-1,2-dicarboxylateYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

4-Methylene-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (12.00 g, 52.80 mmol) was dissolved in MeOH (200 mL) and treated with 4.0 M HCl/dioxane (50 mL) After stirring for 3.5 hours at room temperature, the reaction mixture was concentrated under reduced pressure. The crude residue was dissolved in DCM (200 mL) and treated with DIPEA (22 mL, 127 mmol) and BnOCOCl (9.64 mL, 63.4 mmol). After stirring for 1 hours at room temperature, the reaction mixture was poured into H2O. The aqueous layer was extracted 3× with DCM. The combined organics were dried over MgSO4, filtered and concentrated. The residue was purified by silica column chromatography (10% to 25% EtOAc/hexane) to provide 4-Methylene-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (8.20 g, 56%).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe crude residue was dissolved in DCM (200 mL)
  3. stirringAfter stirring for 1 hours at room temperature
  4. extractionThe aqueous layer was extracted 3× with DCM
  5. dry with materialThe combined organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica column chromatography (10% to 25% EtOAc/hexane)

Sources & evidence

ORD record
ord-7deb621eb37c44208501301ff6fe2a1b
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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