Dichloromethane → Hydrochloric Acid

Participants

Reaction Steps

To a solution of 4-cyanobenzyl alcohol from Step A (153 mg, 0.291 mmol) in 1.0 mL of dichloromethane at -78 ° C. was added diisopropylethylamine (0.066 mL, 0.379 mmol), followed by triflic anhydride (0.053 mL, 0.316 mmol). After 20 minutes, a solution of diketopiperazine from Step F of Example 8 (153 mg, 0.291 mmol) in 1.0 mL dichloromethane was added dropwise via syringe. The reaction was allowed to warm to room temperature over 30 minutes, then concentrated in vacuo. The solution was taken up in 2 mL of methanol and heated to reflux for one hour, then cooled to room temperature, poured into EtOAc, washed with sat, NaHCO3 soln. and brine, dried (Na2SO4), filtered, and concentrated in vacuo to provide the crude product. The product was purified by flash chromatography on silica gel (2-5% MeOH/CH2Cl2), taken up in CH2Cl2 and treated with excess 1M HCl/ether solution, and concentrated in vacuo to provide the titled product hydrochloride (30.8 mg) as a white powder.

Provenance & Evidence