Chloroacetyl chloride → N-(3-bromo-2-(hydroxymethyl)phenyl)-2-chloroacetamide

To a solution of 2-chloroacetyl chloride (380 mg, 3.37 mmol) in DCM (10 mL) was added (2-amino-6-bromophenyl)methanol (630 mg, 3.12 mmol) followed by DIPEA (1.253 mL, 7.17 mmol). The reaction was stirred at room temperature for 3 d. The mixture was diluted with a solution of saturated sodium bicarbonate (15 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried over sodium sulfate and concentrated to give N-(3-bromo-2-(hydroxymethyl)phenyl)-2-chloroacetamide. The above product was dissolved in IPA (10 mL), and added 50% w/w aqueous NaOH (374 mg, 4.68 mmol). The mixture was stirred at room temperature for 3 h and concentrated. The residue was diluted with a solution of saturated sodium bicarbonate (15 mL) and extracted with DCM (80 mL). The organic layer was dried over sodium sulfate and concentrated to give 6-bromo-3,5-dihydrobenzo[e][1,4]oxazepin-2(1H)-one. The above intermediate was dissolved in THF (60 mL) and added 2.0 M borane dimethyl sulfide methyl sulfide complex in THF (6.24 mL, 12.47 mmol). The reaction was refluxed for 60 min, cooled to room temperature, and added MeOH (5.0 mL) dropwise. The mixture was refluxed for 30 min concentrated. The residue was diluted with a solution of saturated sodium bicarbonate (60 mL) and extracted with ethyl acetate (60 mL). The organic layer was dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (0-100% ethyl acetate:hexanes) to afford the title compound (237 mg, 32% yield) as clear gum. LCMS, [M+H]+=229.9. 1H NMR (400 MHz, CDCl3) δ 7.13 (dd, J=7.9, 1.1 Hz, 1H), 6.94 (t, J=7.9 Hz, 1H), 6.74 (dd, J=7.9, 0.9 Hz, 1H), 4.92 (s, 2H), 4.06 (br. s., 1H), 3.89-3.81 (m, 2H), 3.24-3.17 (m, 2H).

1. extractionextracted with ethyl acetate (20 mL)
2. dry with materialThe organic layer was dried over sodium sulfate
3. concentrationconcentrated

ORD record

ord-d1d6f2adf2ce423b9b2e274864bf14c9

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062028B2