Hydrochloric Acid → 4-Methoxymethyl-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester

HRID 417677Notes

Reaction equation

HRID 417677 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([CH2:10][O:11][CH3:12])[CH2:7][N:6]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:4].[Li+].[OH-].Cl.BrC[C:25]([C:27]1[CH:32]=[CH:31][C:30]([Br:33])=[CH:29][CH:28]=1)=[O:26].C(N(CC)CC)C>CO>[C:16]([O:15][C:13]([N:6]1[CH2:7][CH:8]([CH2:10][O:11][CH3:12])[CH2:9][CH:5]1[C:3]([O:2][CH2:1][C:25]([C:27]1[CH:32]=[CH:31][C:30]([Br:33])=[CH:29][CH:28]=1)=[O:26])=[O:4])=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 74544-Bromophenacyl bromideHCID 8471TriethylamineHCID 66621318O1-tert-butyl O2-methyl 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate

Product 1

HCID 666207834-Methoxymethyl-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl esterYield 97.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-Methoxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (461 mg, 1.68 mmol) was dissolved in MeOH (17 mL) and LiOH (1 M in H2O, 8.5 mL, 8.5 mmol) was added. After stirring at RT for 5 h, the MeOH was removed under reduced pressure. The aqueous solution was poured into a separatory funnel, diluted with 1 M HCl (9 mL, 9 mmol) and extracted with DCM (3×). The combined organics were dried over MgSO4, filtered and concentrated. The residue was dissolved in MeCN (17 mL) and treated with 2,4′-dibromoacetophenone (514 mg, 1.85 mmol), and triethylamine (0.258 mL, 1.85 mmol). After stirring for 2 h, the solvent was removed and the solid was suspended in EtOAc. The organic layer was washed with saturated aqueous NaHCO3 and brine then dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (15% to 35% EtOAc/Hex) to afford the title compound (746 mg, 97%).

Workup

  1. customthe MeOH was removed under reduced pressure
  2. additionThe aqueous solution was poured into a separatory funnel
  3. extractionextracted with DCM (3×)
  4. dry with materialThe combined organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in MeCN (17 mL)
  8. stirringAfter stirring for 2 h
  9. customthe solvent was removed
  10. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
  11. dry with materialthen dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude residue was purified by silica column chromatography (15% to 35% EtOAc/Hex)

Sources & evidence

ORD record
ord-447e37ce536c4d889bd3160fa4b2532e
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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