Phosgene → HCID 131733860, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3D (303 mg, 0.382 mmol) in acetonitrile (7 mL) and dichloromethane (4 mL) at 0° C., was added phosgene solution (20% in toluene) (0.241 mL, 0.458 mmol) dropwise. The mixture was stirred at 0° C. for 40 min, then at rt for 10 min while extra phosgene was removed by bubbling Ar. The resulting solution was added dropwise via syringe pump into a solution of TEA (0.426 mL, 3.05 mmol) in dichloromethane (120 mL) at rt over 3.0 h. The solution was stirred at rt for additional 45 min. Solvent was removed and the crude was purified by prep HPLC to give a mixture of diastereoisomer (237 mg). The diastereoisomers were separated by chiral HPLC ((R,R)-Whelk-01 250×21.1 mm column) to give 3E (100 mg, 63.9% yield). MS (ESI) m/z: 820 [M+1]+; 1H NMR (400 MHz, chloroform-d) δ ppm 1.29-1.41 (m, 24H) 2.21 (s, 3H) 3.18-3.33 (m, 2H) 3.33-3.39 (m, 3H) 3.38-3.48 (m, 1H) 3.95 (dd, J=10.77, 4.17 Hz, 1H) 4.28 (d, J=17.58 Hz, 1H) 4.67 (t, J=11.21 Hz, 1H) 5.43 (d, J=5.71 Hz, 1H) 5.65 (d, J=17.58 Hz, 1H) 6.39-6.48 (m, 2H) 6.63 (s, 1H) 6.76 (d, J=8.35 Hz, 1H) 6.85 (s, 1H) 7.03 (d, J=9.23 Hz, 1H) 7.08 (s, 1H) 7.50 (d, J=7.91 Hz, 1H) 7.56-7.65 (m, 2H) 7.85 (d, J=8.35 Hz, 1H) 8.05 (s, 1H). 19F NMR (376 MHz, chloroform-d) δ ppm −141.30 (br. s., 1F).

Provenance & Evidence