Sodium Carbonate → HCID 59118256, compound

Temperature

80 °C

3,4-Dichlorophenylboronic acid (34 mg, 0.18 mmol), a solution of palladium acetate (3 mg, 0.01 mmol) and triphenylphosphine (12 mg, 0.05 mmol) in toluene (1 mL), and 2 M aqueous sodium carbonate (1 mL) were added successively to a solution of tert-butyl (2R)-2-hydroxy-2-(3-pyridinyl)ethyl{[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}carbamate (Example 37, 60 mg, 0.12 mmol) in toluene (2 mL). The mixture was heated (80° C.) and stirred for 16 hours. After cooling the reaction was diluted with dichloromethane (5 mL) and the layers were separated. The organic layer was concentrated in vacuo and the residue was dissolved in a solution of 4 M hydrogen chloride in dioxane (4 mL). The solution was stirred for 16 hours and then concentrated in vacuo. Preparative reverse phase HPLC of the residue using acetonitrile/water afforded 10.3 mg (20%) of the desired product (retention time=2.19 min.): 1H NMR (CD3OD, δ): 8.71 (d, J=2.2 Hz, 1H), 8.59 (dd, J=5.1, 1.5 Hz, 1H), 8.11 (ddd, J=7.9, 1.7, 1.7 Hz, 1H), 7.71 (d, J=2.3 Hz, 1H), 7.61 (dd, J=7.9, 5.1 Hz, 1H), 7.37-7.56 (m, 4H), 6.99 (d, 9.2 Hz, 1H), 5.22 (dd, J=10.5, 2.9 Hz, 1H), 4.43-4.54 (m, 1H), 3.26-3.55 (m, 4H), 2.87-3.10 (m, 2H), 2.11-2.22 (m, 1H), 1.76-1.92 (m, 1H); mass spectroscopy gave m/z=429.2 [M+H]+.

1. temperatureAfter cooling the reaction
2. customthe layers were separated
3. concentrationThe organic layer was concentrated in vacuo
4. dissolutionthe residue was dissolved in a solution of 4 M hydrogen chloride in dioxane (4 mL)
5. stirringThe solution was stirred for 16 hours
6. concentrationconcentrated in vacuo

ORD record

ord-1a2f8c0b70634dae959342212f9df9c1

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06660752B2