4-Methylmorpholine → 1,1-Dimethylethyl (2S)-2-[(methoxymethylamino)carbonyl]-1-pyrrolidinecarboxylate

HRID 1738773Notes

Reaction equation

HRID 1738773 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[CH3:17][NH:18][O:19][CH3:20].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>ClCCl>[CH3:17][N:18]([O:19][CH3:20])[C:10](=[O:12])[C@@H:9]1[CH2:13][CH2:14][CH2:15][N:8]1[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 6882981,1-Dimethylethyl (2S)-2-[(methoxymethylamino)carbonyl]-1-pyrrolidinecarboxylateYield 63.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 30 g Boc-proline and 13.6 g N,O-dimethylhydroxylamine hydrochloride in 250 ml of dichloromethane was added 26.73 g 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, 18.83 g N-hydroxy-benzotriazol and 49.34 g N-methyl-morpholine at 0° C. The mixture was stirred overnight at room temperature. The reaction mixture was washed sequentially with saturated sodium bicarbonate, a 5% aqueous solution of citric acid and brine. The organic phase was dried over sodium sulfate. After filtration, the solvent was removed in vacuo to give 22.9 g N-methyl-N-methoxy-(Boc-proline)-amide.

Workup

  1. washThe reaction mixture was washed sequentially with saturated sodium bicarbonate
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationAfter filtration
  4. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-9c9d4f3043ce4e7da5612e117a88c409
Source dataset
uspto-grants-1999_10
Patent number
US05965537

Reaction notes

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