Hydrochloric Acid → HCID 90082651, compound

Participants

Reaction Conditions

Reaction Steps

A dried 200 mL round bottom was charged with boron trichloride (1.0 M PhMe) (4.67 mL, 4.67 mmol) and cooled to 0° C. for 15 min. Next, 3,4-dihydro-2H-benzo[b][1,4]oxazine (574 mg, 4.25 mmol) in toluene (Volume: 9.4 mL) was added dropwise over about 5 min, and then the solution was stirred for 10 minutes. Aluminum chloride (623 mg, 4.67 mmol) was added and the solution was stirred for 5 minutes. Then, 3-methylbenzonitrile (0.605 mL, 5.10 mmol) was added. The reaction mixture was stirred at 0° C., for about 1 h, then allowed to warm to room temperature and heated to reflux for 8 h. HCl (1.5 M) (28.3 mL, 42.5 mmol) was added, and the reaction mixture was heated to reflux for 2 h. The reaction mixture was cooled to room temperature, basified to pH 9 with 1 M NaOH, and extracted three times with CH2Cl2. The organic layers were dried with MgSO4 and evaporated. The residue was purified via ISCO (40 g column; hex/EtOAc; 2 min, 0%, 27 min, 40%, 30 min 40%;) to afford (3,4-dihydro-2H-benzo[b][1,4]oxazin-5-yl)(m-tolyl)methanone, Intermediate C-1A (0.73 g, 2.9 mmol, 68%)1H NMR (400 MHz, chloroform-d) δ 8.31 (br. s., 1H), 7.47-7.39 (m, 2H), 7.37-7.33 (m, 2H), 7.12 (dd, J=8.1, 1.5 Hz, 1H), 6.99-6.88 (m, 1H), 6.48 (t, J=7.9 Hz, 1H), 4.29 (t, J=4.5 Hz, 2H), 3.63 (td, J=4.6, 2.8 Hz, 2H), 2.43 (s, 3H).

Provenance & Evidence