1,2-Dichloroethane → Methyl ({[1-({[tert-butyl-(dimethyl)silyl]oxy}methyl)cyclopropyl]methyl}amino)acetate

Participants

Reaction Steps

To a stirred solution of 1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropanecarbaldehyde (5.0 g, 0.023 mol) in anhydrous 1,2-dichloroethane (113 mL, 1.44 mol) was added glycine methyl ester, hydrochloride (2.92 g, 0.0232 mol), TEA (6.53 mL, 0.0466 mol), and sodium triacetoxyborohydride (10.4 g, 0.0467 mol). The resulting mixture was stirred at RT for 1 h. LC/MS data indicated that the reductive amination was complete to afford methyl ({[1-({[tert-butyl-(dimethyl)silyl]oxy}methyl)cyclopropyl]methyl}amino)acetate. LC-MS: 288.2 (M+1H)+. To the crude reaction mixture was added benzaldehyde (2.8 mL, 0.028 mol), followed by a second aliquot of sodium triacetoxyborohydride (6 g). After stirring at RT for 2 h, the reaction was quenched by the addition of saturated aqueous NaHCO3. The organic layer was separated and washed with brine, then dried (MgSO4), and concentrated in vacuo. The crude product (9.1 g) was purified by Combiflash chromatography (120 g silica gel column, 0-15% EtOAc/hexanes 20 min), to afford the desired product as an oil (4.6 g). LC/MS: 378.2 (M+1H)+.

Provenance & Evidence