1-Hydroxybenzotriazole → Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate

HRID 1894993Notes

Reaction equation

HRID 1894993 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:17][NH:18][O:19][CH3:20].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[N:18]([O:19][CH3:20])[CH3:17])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27605291-((Tert-butoxy)carbonyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 57419605Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylateYield 72.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (3.00 g, 13.93 mmol), N,O-dimethylhydroxylamine hydrochloride (1.63 g, 16.72 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.94 g, 15.32 mmol) and 1-hydroxybenzotriazole (2.07 g, 15.32 mmol) were placed in a 100 mL round bottomed flask and dissolved in DMF (30 mL). Diisopropylethylamine (6.1 mL, 34.82 mmol) was slowly added, and the reaction mixture was stirred at room temperature for 24 hours. The reaction was quenched by addition of water and extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over MgSO4, filtered and evaporated under reduced pressure to give 2.60 g (72% yield) of 3-(methoxy-methyl-carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow oil which was used in the next step without further purification.

Workup

  1. customThe reaction was quenched by addition of water
  2. extractionextracted with ethyl acetate
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-7975184a756a43c29601533de1707b7d
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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