3-CARBOXYMETHOXY-AZETIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER synthesis

Yield:-

Reaction Conditions:

Stage #1: tert-butyl 3-hydroxyazetidine-1-carboxylatewith sodium hydride in N,N-dimethyl-formamide at 0; for 0.25 h;
Stage #2: monosodium iodoacetate in N,N-dimethyl-formamide at 20; for 65 h;
Stage #3: with hydrogenchloride in water; pH=2;

Steps:

17

Preparation 17; S-Carboxymethoxyazetidine-l-carboxylic acid tert-butyl ester; Anhydrous DMF (5 mL) was added slowly to a stirred mixture of 3-hydroxyazetidine-l- 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 0⁰C. After 15 min, ICH₂CO₂Na (630 mg, 3.0 mmol) was added, then stirring was continued at 20⁰C 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 x 10 mL), then the combined aqueous extracts were acidified to pH 2 with 2 M HCl, before being extracted with EtOAc (2 x 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

References:

WO2006/67532,2006,A1 Location in patent:Page/Page column 25