Acetonitrile → 4-(6-Bromo-benzothiazol-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (7.02 g, 34.9 mmol) in THF (67.1 ml) at 0° C. was added NaH (0.915 g, 95%, 36.2 mmol). Upon completion of addition, the reaction mixture was warmed to rt, where it stirred for 30 minutes. A solution of 6-bromo-2-chlorobenzo[d]thiazole (6.67 g, 26.8 mmol) in THF (30 mL) was then added and the resulting mixture was heated to 50° C., where it stirred overnight. At the conclusion of this period, the solvent was removed under reduced pressure to yield a residue. CH3CN (167 mL) was added to the residue, and the resulting mixture was stirred for 20 min. After this time, H2O (233 mL) was added, and the resulting mixture was stirred at rt for 10 min. The resulting precipitate was collected by filtration. The resulting solid was rinsed with cool CH3CN—H2O (3×20 mL, 1:2, v/v) and then dried in vacuum to afford Compound 1A as a white solid (10.5 g, 25.3 mmol, 94% yield. HPLC purity is 100%). 1H NMR (500 MHz, chloroform-d) δ ppm 7.77 (d, J=1.9 Hz, 1H), 7.49-7.54 (m, 1H), 7.44-7.49 (m, 1H), 5.35 (ddd, J=7.6, 4.1, 3.9 Hz, 1H), 3.68-3.82 (m, 2H), 3.31-3.43 (m, 2H), 2.01-2.15 (m, 2H), 1.88 (dddd, J=12.6, 8.4, 4.1, 3.9 Hz, 2H), 1.48 (s, 9H).

1. additionUpon completion of addition
2. temperaturethe resulting mixture was heated to 50° C.
3. stirringwhere it stirred overnight
4. customAt the conclusion of this period, the solvent was removed under reduced pressure
5. customto yield a residue
6. stirringthe resulting mixture was stirred for 20 min
7. stirringthe resulting mixture was stirred at rt for 10 min
8. filtrationThe resulting precipitate was collected by filtration
9. washThe resulting solid was rinsed with cool CH3CN—H2O (3×20 mL, 1:2
10. customv/v) and then dried in vacuum

ORDレコード

ord-d74ce37c8bbb43679331de45fdba803b

出典データセット

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08940716B2