4-Methylmorpholine → D-1-N-Boc-prolinamide

HRID 2243878Notes

Reaction equation

HRID 2243878 reaction equation
C[N:2]1CCOCC1.ClC(OCC(C)C)=O.[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[C:28]([OH:30])=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].[OH-].[NH4+]>C1COCC1>[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[C:28](=[O:30])[NH2:2])=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 2756826D-1-N-Boc-prolinamideYield 54.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.33 g, 97.5 mmol) was added to (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (20.0 g, 92.9 mmol) in THF (200 mL) at −78° C. and stirred for 1 h. Ammonium hydroxide (58 mL) was added slowly as the reaction warmed up to RT and stirred for a further 2 h. The reaction mixture was partitioned between DCM and water. The organic extracts were washed with 1 M HCl, dried over sodium sulphate, filtered and concentrated to afford the title product (10.8 g, 54%) as a colourless semisolid.

Workup

  1. stirringstirred for a further 2 h
  2. customThe reaction mixture was partitioned between DCM and water
  3. washThe organic extracts were washed with 1 M HCl
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-14bc45ad321e40aeaecc5f402cf297d9
Source dataset
uspto-grants-2010_03
Patent number
US07678796B2

Reaction notes

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