Sodium hydride → 1-Azetidinecarboxylic acid, 3-(2-oxo-1-pyrrolidinyl)-, 1,1-dimethylethyl ester

HRID 1945543Notes

Reaction equation

HRID 1945543 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][C:13](=[O:18])[CH2:14][CH2:15][CH2:16]Cl)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:12]2[CH2:16][CH2:15][CH2:14][C:13]2=[O:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 59605845HCID 59605845, compound

Product 1

HCID 596061821-Azetidinecarboxylic acid, 3-(2-oxo-1-pyrrolidinyl)-, 1,1-dimethylethyl esterYield 35.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(4-chlorobutyrylamino)azetidine-1-carboxylic acid tert-butyl ester (1.04 g, 3.76 mmol) in DMF (15 mL) was cooled to 0° C. before the addition of NaH (180 mg, 4.51 mmol). The resulting mixture was allowed to stir for 2 h then quenched with H2O and extracted with EtOAc. The organic phase was washed with H2O and brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 20-100%) affording 3-(2-Oxopyrrolidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as a brown oil (320 mg, 35%). 1H NMR (CDCl3, 300 MHz): δ 4.99 (m, 1 H), 4.15 (m, 2 H), 3.97 (m, 2 H), 3.57 (t, J=7.0 Hz, 2 H), 2.42 (t, J=8.1 Hz, 2 H), 2.15-2.02 (m, 2 H) and 1.45 (s, 9 H)

Workup

  1. customthen quenched with H2O
  2. extractionextracted with EtOAc
  3. washThe organic phase was washed with H2O and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 20-100%)

Sources & evidence

ORD record
ord-eaf5f0ccf2f245138b998bb146419638
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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