Phosgene → HCID 131733868, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 19A (135 mg, 0.168 mmol) in acetonitrile (6 mL) and dichloromethane (3 mL) at 0° C., was added phosgene solution (20% in toluene, 0.106 mL, 0.201 mmol) dropwise. The mixture was stirred at 0° C. for 40 min, then at rt for 10 min. Extra phosgene was removed by bubbling Ar for 20 min. The crude was redissolved in acetonitrile (1.0 mL) and dichloromethane (1.0 mL), and was added dropwise via syringe pump into a solution of TEA (0.187 mL, 1.340 mmol) in dichloromethane (60 mL) at rt over 3.0 h. The solution was stirred at rt over night. The solvent was removed and the crude residue was purified using a prep HPLC equipped with a C18 PHENOMENEX® Luna Axia column (30 mm×75 cm, 5μ). The desired fractions were collected and concentrated to give a mixture of diastereoisomers (114 mg). The diastereoisomers were separated by a prep chiral HPLC [(R,R)-Whelk-01 250×21.1 mm column] to give 19B (48 mg, 0.058 mmol, 34.4% yield). MS (ESI) m/z: 832.6 (M+H)+.

Provenance & Evidence