Acetone → (1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexanecarboxylic acid

Participants

Reaction Steps

A stirring solution of (1R,2S,5R)-5-amino-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)cyclohexanecarboxylic acid (TFA salt, 35.5 g, 0.0725 mol) in dichloroethane (350 mL) was charged sequentially with N-methylmorpholine (29.3 g, 4.0 eq) and acetone (42.05 g, 10 eq). The mixture was stirred at room temperature for 10 min. and sodium triacetoxyborohydride (30.7 g, 2 eq) was added at 0° C. The mixture was stirred at room temperature for 14 h, then formaldehyde (37 wt % solution, 28.4 g, 5 eq) and sodium triacetoxyborohydride (18.4 g, 1.2 eq) were added. The mixture was stirred at room temperature for 2 h. Water (70 ml) was added and the stirring was continued for 10 minutes. The mixture was concentrated under reduced pressure to remove the organic solvents. The resulting mixture was adjusted pH to 7-8 with saturated NaHCO3 solution and then to pH˜6 with 1 N HCl. The mixture was extracted with dichloromethane (5×250 ml). The extracts were combined, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was dissolved in dichloromethane (100 ml) and the resultant solution was added dropwise to diethyl ether (1500 ml) with stirring. The solid formed was collected with filtration and washed with diethyl ether (3×50 ml). The white solid was dried in vacuo to give (1R,2S,5R)-2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexanecarboxylic acid (31 g, 99%). The compound was used in the next step without further purification. LC/MS found [M+H]+=432.

Provenance & Evidence