1,1'-Carbonyldiimidazole → Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate

HRID 2384929Notes

Reaction equation

HRID 2384929 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH:22]([C:25]([OH:27])=O)[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].Cl.[CH3:29][NH:30][O:31][CH3:32]>ClCCl>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH:22]([C:25](=[O:27])[N:30]([O:31][CH3:32])[CH3:29])[CH2:21]1)=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27605291-((Tert-butoxy)carbonyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 57419605Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylateYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add portionwise 1,1′-carbonyldiimidazole (4.14 g, 25.6 mmol) to a solution of pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (5.0 g, 23.2 mmol) in dichloromethane (77 mL) at RT. Allow the mixture to stir for 15 min. Add slowly N,O-dimethylhydroxylamine hydrochloride (2.7 g, 27.9 mmol). Stir the reaction mixture at RT overnight. Dilute the mixture with dichloromethane (200 mL), wash with water (2×300 mL), brine (200 mL), dry over Na2SO4, filter, and concentrate. Purify the crude material by flash chromatograph, eluting with 50-100% ethylacetate/hexane to give 5.36 g (89%) of the title compound. LC-MS/ES m/z 203.0 [M−tertBu+H]+.

Workup

  1. stirringStir the reaction mixture at RT overnight
  2. washwash with water (2×300 mL), brine (200 mL)
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude material by flash chromatograph
  7. washeluting with 50-100% ethylacetate/hexane

Sources & evidence

ORD record
ord-396d65e48c1f4da98c5dfed3dc1064d4
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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