Acetic Acid → [3-(2-Hydroxy-ethyl)-benzyl]-(3-propoxy-propyl)-carbamic acid tert-butyl ester

Participants

Reaction Steps

A mixture (3-formyl-phenyl)-acetic acid ethyl ester (530 mg), (3-propoxypropyl)amine (1.5 g) and acetic acid (0.17 mL) in methanol (15 mL) was stirred at room temperature for 15 minutes. Sodium triacetoxyborohydride (950 mg) was added. After 5 hours, the reaction mixture was neutralised with aqueous ammonia (0.880) and the solution evaporated to dryness. The residue was diluted with toluene and the mixture evaporated. The resulting gum was dissolved in methanol and applied to a SCX cartridge (70 g, varian). The cartridge was eluted with methanol (250 mL) and then 20% ammonia in methanol to collect the reductive amination product. Toluene was added and the solution was evaporated. The crude product was dissolved in dichloromethane (20 mL) and di-tert-butyl dicarbonate (1.8 g) added. After 16 hours, the solution was evaporated, the residue dissolved in ethanol (30 mL), anhydrous calcium chloride (11.0 g) added, followed by portionwise addition of sodium borohydride (700 mg). After 16 hours, the reaction mixture was quenched with 2M aqueous potassium carbonate (20 mL), filtered and evaporated. The residue was partitioned between ethyl acetate and brine. The organic solution was dried over sodium sulphate, filtered and evaporated. Purification was by silica gel chromatography eluting with ethyl acetate:dichloromethane 1:4 to give the subtitle compound (300 mg).

Provenance & Evidence