Phenylboronic Acid → 3-Phenyloxan-4-one

Temperature

0 °C

To a stirred mixture of phenylboronic acid (16.81 g, 138 mmol), trans-2-Aminocyclohexanol hydrochloride (1.393 g, 9.19 mmol), and Nickel(II) chloride hexahydrate (1.092 g, 4.59 mmol) in THF (92 mL) at 0° C. was added Sodium bis(trimethylsilyl)amide (1.0 M in THF) (184 mL, 184 mmol) dropwise over 10 min. When the addition was complete, the reaction mixture was sparged with N2 for 15 min. To the reaction mixture at 0° C. was then added 2-Propanol (375 mL)(previously sparged with N2). The resulting mixture was allowed to come to RT at which time 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Intermediate I(1)) (25 g, 92 mmol) was added dropwise over 5 min. The reaction mixture was then brought to 60° C. and stirred overnight. The reaction mixture was then cooled to 0° C. and quenched by the careful addition of aqu. 1 N HCl until acidic. The resulting mixture was extracted with EtOAc (3×150 mL). The combined organic extracts were washed with Brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography (Silica, EtOAc/Hexanes) gave 3-phenyldihydro-2H-pyran-4(3H)-one (8.37 g, 47.5 mmol, 51.7% yield) as a slightly orange oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.26-7.31 (1H, m), 7.21-7.26 (2H, m), 4.17-4.31 (2H, m), 3.91-4.05 (2H, m), 3.78 (1H, dd, J=8.55, 6.10 Hz), 2.61-2.74 (1H, m), 2.51-2.61 (1H, m).

1. additionWhen the addition
2. customthe reaction mixture was sparged with N2 for 15 min
3. customat 0° C.
4. customadded 2-Propanol (375 mL)(previously sparged with N2)
5. additionwas added dropwise over 5 min
6. customwas then brought to 60° C.
7. customquenched by the careful addition of aqu
8. extractionThe resulting mixture was extracted with EtOAc (3×150 mL)
9. washThe combined organic extracts were washed with Brine (100 mL)
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customPurification by flash chromatography (Silica, EtOAc/Hexanes)

ORD record

ord-3ec9746ca02243b3a757e9d1275a8381

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486952B2