反应详情

2,3,4,5-tetrahydro-1,4-benzoxazepin-7-ylboronic acid hydrochloride salt (188 mg, 0.82 mmol) was taken into 50% aqueous THF (2 mL) followed by addition of solid sodium bicarbonate (360 mg, 4.3 mmol) then 4-(fluoromethyl)piperidine-1-carbonyl chloride (reagent preparation 37) (218 mg, 1.21 mmol) in a minimum of THF. The mixture was stirred at room temperature over 1 h then partitioned with 0.5M aqueous hydrochloric acid and ethyl acetate. The organic solution was then brine washed, dried over anhydrous sodium sulfate, filtered and concentrated. The residue obtained was taken into isopropyl acetate and extracted once with 1M aqueous sodium hydroxide. The aqueous solution was then acidified to pH 2 using concentrated hydrochloric acid and extracted once with ethyl acetate then brine washed, dried over anhydrous sodium sulfate, filtered and concentrated to provide (4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (143 mg, 52% yield) as an amorphous residue. MS (EI) for C16H22BrFN2O4: 337 (MH+).

1. customthen partitioned with 0.5M aqueous hydrochloric acid and ethyl acetate
2. washbrine washed
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue obtained
7. extractionextracted once with 1M aqueous sodium hydroxide
8. extractionextracted once with ethyl acetate
9. washbrine washed
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated