Potassium Carbonate → Ethyl 4-(4-((2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)piperidin-1-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

Ethyl 4-(4-methylenepiperidin-1-yl)benzoate 390C (145.8 mg, 0.594 mmol) was taken up with 0.5M THF solution of 9-BBN (1.189 mL, 0.594 mmol) under nitrogen and stirred at 75° C. for 1 h. The reaction mixture was then added to a suspension of 6-bromo-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one 19 (144 mg, 0.594 mmol), PdCl2(dppf)-CH2Cl2 adduct (14.56 mg, 0.018 mmol) and potassium carbonate (164 mg, 1.189 mmol) in DMF (2.0 mL) and water (0.2 mL) and stirred at 60° C. The reaction was pulled, cooled to RT, and diluted with water (10 mL) and EtOAc (10 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL); the organic layer was separated and washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. Flash column chromatography (10%-20%-30% EA/Hex) provided the desired product as an off-white solid (62 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09-1.32 (m, 6H) 1.35-1.46 (m, 2H) 1.56-1.76 (m, 3H) 2.43 (d, J=6.82 Hz, 2H) 2.77 (t, J=11.75 Hz, 2H) 3.82-3.96 (m, 2H) 4.22 (q, J=7.07 Hz, 2H) 4.56-4.66 (m, 1H) 6.63-6.77 (m, 2H) 6.86 (d, J=8.08 Hz, 1H) 6.94 (d, J=9.09 Hz, 2H) 7.69-7.82 (m, 2H) 10.59 (s, 1H). ESI-MS: m/z 409.4 (M+H)+.

Provenance & Evidence