Phosgene → HCID 118098701, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 8C (228 mg, 0.282 mmol) in acetonitrile (10 mL) and dichloromethane (5 mL) at 0° C., was added phosgene solution (20% in toluene) (0.178 mL, 0.339 mmol) dropwise. The mixture was stirred at 0° C. for 20 min, then at rt for 15 min. The extra phosgene was removed by bubbling Ar though the reaction mixture (15 min). The resulting solution was added dropwise via syringe pump into a stirred solution of TEA (0.315 mL, 2.258 mmol) in dichloromethane (80 ml) at rt over 3.0 h. The reaction was quenched by 0.5 N HCl and extracted with CH2Cl2. The organic layer was collected, washed with water and dried over sodium sulfate, then concentrated. The crude product was purified by flash chromatography to give a mixture of diastereoisomers (235 mg). The diastereomers (165 mg) were separated by a prep chiral HPLC (R,R-Whelk-O column 21.1×250 mm) to give 8D (54 mg, 0.065 mmol, 32.7% yield). MS (ESI) m/z: 883 [M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 1.26 (d, J=6.59 Hz, 3H) 1.28-1.37 (m, 21H) 1.42 (d, J=6.59 Hz, 3H) 2.09 (s, 3H) 3.27-3.42 (m, 5H) 3.90 (dd, J=10.77, 3.73 Hz, 1H) 4.30 (d, J=17.58 Hz, 1H) 4.63 (t, J=10.99 Hz, 1H) 5.43 (d, J=5.71 Hz, 1H) 5.68 (d, J=18.02 Hz, 1H) 6.36 (s, 1H) 6.55 (d, J=5.71 Hz, 1H) 6.75 (d, J=8.35 Hz, 1H) 6.86 (s, 1H) 7.01 (d, J=9.23 Hz, 1H) 7.04-7.12 (m, 2H) 7.45-7.54 (m, 2H) 7.61 (d, J=7.91 Hz, 1H) 7.77 (d, J=8.35 Hz, 1H) 8.03 (s, 1H). 19F NMR (376 MHz, chloroform-d) δ ppm −141.12 (br. s., 1F).

Provenance & Evidence