Water → HCID 58371984, compound

HRID 1020932Notes

Reaction equation

HRID 1020932 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1([OH:22])[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:8]1)=[O:6].[CH3:23]I.O>CN(C=O)C>[CH3:3][O:4][C:5]([C:7]1([O:22][CH3:23])[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:8]1)=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58371997HCID 58371997, compound

Product 1

HCID 58371984HCID 58371984, compoundYield 98.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
17 °C

Procedure

To a suspension of NaH (52 g, 1.3 mol) in 2.2 L of anhydrous DMF at 8° C., was added a solution of 3-Hydroxy-pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester 3a (278 g, 1.0 mol) in 700 DMF, keeping the reaction temperature below 11° C. After complete addition (˜20 min), ice bath was removed, stirred at 16-18° C. for 1 h, and then at ambient temperature for 1 h. Cooled back to 15° C., added MeI (81 mL, 1.3 mol) slowly. Reaction mixture was stirred at ambient temperature for 1 overnight. The reaction mixture was then poured in a cold water (4 L) and then extracted with Et2O (6 L) and EtOAc (2 L), washed the organic later with water (5 L), brine (700 mL), dried over magnesium sulfate, filtered and evaporated to give crude 3-Methoxy-pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester 4a 289 g (99% crude yield, contains mineral oil) (stirring/separation with pentane wash gave 4a, 268.2 g (92%).

Workup

  1. customthe reaction temperature below 11° C
  2. additionAfter complete addition (˜20 min), ice bath
  3. customwas removed
  4. waitat ambient temperature for 1 h
  5. temperatureCooled back to 15° C.
  6. customReaction mixture
  7. stirringwas stirred at ambient temperature for 1 overnight
  8. extractionextracted with Et2O (6 L) and EtOAc (2 L)
  9. washwashed the organic later with water (5 L), brine (700 mL)
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-ea38cde443c846c787912b57126a4513
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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