Trimethylaluminum → 3-(4-{[5-(4-Chloro-phenyl)-3-(2-hydroxy-ethyl)-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

Dissolve 3-(4-amino-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (2.27 mmol, 667 mg) in toluene (35 mL) and add 2M trimethylaluminum in toluene (2.27 mmol 1.13 mL). Add to this solution 2-(4-chloro-phenyl)-4,5-dihydro-thieno[2,3-c]pyran-7-one (1.51 mmol 400 mg) and heat the reaction at 80° C. for 5 h. Cool the reaction to room temperature and slowly quench with 10 mL of saturated Rochelle's salt. Stir the mixture for 10 min and dilute with 40 mL of water. Separate the organic portion and extract the aqueous portion with EtOAc (2×25 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Purify by chromatography (hexane to 70% ethyl acetate/hexane) to afford 840 mg (99%) of the title compound. MS/ES m/z (35Cl) 557.0 [M−H]−.

Provenance & Evidence