Sodium hydride → {[1-(tert-Butoxycarbonyl)azetidin-3-yl]oxy}acetic acid

HRID 217175Notes

Reaction equation

HRID 217175 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH2:16][C:17]([O:19][Na])=[O:18]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][CH2:16][C:17]([OH:19])=[O:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 178521101HCID 178521101, compound

Product 1

HCID 40429408{[1-(tert-Butoxycarbonyl)azetidin-3-yl]oxy}acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Anhydrous DMF (5 mL) was added slowly to a stirred mixture of 3-hydroxyazetidine-1-carboxylic acid tert-butyl ester (350 mg, 2.0 mmol) and NaH (121 mg of a 60% dispersion in mineral oil, 3.0 mmol) at 0° C. After 15 min, ICH2CO2Na (630 mg, 3.0 mmol) was added, then stirring was continued at 20° C. for 65 h. The solvent was removed in vacuo, then the residue was partitioned between H2O (15 mL) and EtOAc (10 mL). The organic phase was extracted with saturated aqueous Na2CO3 (2×10 mL), then the combined aqueous extracts were acidified to pH 2 with 2 M HCl, before being extracted with EtOAc (2×50 mL). The EtOAc extracts were washed with brine, before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (IH-EtOAc, 1:1) furnished the title compound. δH (CDCl3): 1.45 (s, 9H), 3.90-4.00 (m, 2H), 4.10-4.19 (m, 4H), 4.36-4.42 (m, 1H), 10.10-10.30 (br s, 1H).

Workup

  1. waitwas continued at 20° C. for 65 h
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned between H2O (15 mL) and EtOAc (10 mL)
  4. extractionThe organic phase was extracted with saturated aqueous Na2CO3 (2×10 mL)
  5. extractionbefore being extracted with EtOAc (2×50 mL)
  6. washThe EtOAc extracts were washed with brine
  7. dry with materialbefore being dried (MgSO4)
  8. filtrationFiltration, solvent evaporation, and column chromatography (IH-EtOAc, 1:1)

Sources & evidence

ORD record
ord-a85675f0e77d45daa091e4a43914b6ef
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

Loading…