Hydrochloric Acid → 6-Bromo-2,3,4,5-tetrahydro-1H-1-benzazepine

To a solution of (E)-5-bromo-3,4-dihydronaphthalen-1(2H)-one oxime (1.41 g, 5.87 mmol) in DCM (20 mL) at −10° C. under nitrogen was slowly added a solution of 1.0 M DIBAL-H in hexane (35.2 mL, 35.2 mmol). Upon completion of addition, the reaction mixture was stirred at room temperature for 2 h. After this time, the reaction mixture was cooled to 0° C. and then sodium fluoride (7.40 g, 176 mmol) and water (3.0 mL) were slowly added. The resulting mixture was stirred at 0° C. for 30 min and then CELITE® was added. The mixture was filtered and rinsed with DCM (100 mL). The filtrate was dried over anhydrous Na2SO4, filtered, and concentrated to provide the crude product. The crude product was converted to the HCl salt with aqueous 1.0 N HCl (3.0 mL) and then purified by preparative HPLC (PHENOMENEX® Axia Luna 5μ C18 30×100 mm; 10 min gradient from 80% A:20% B to 0% A:100% B and 5 min 100% B (A=90% H2O/10% MeOH+0.1% TFA); (B=90% MeOH/10% H2O+0.1% TFA); detection at 220 nm). The purified product was free based with a solution of saturated sodium bicarbonate (15 mL) and was then extracted with ethyl acetate (20 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford the title compound (612 mg, 45% yield). LCMS, [M+Na]+=236.0. 1H NMR (400 MHz, MeOD) δ 7.12 (dd, J=7.8, 1.4 Hz, 1H), 6.88 (t, J=7.8 Hz, 1H), 6.83 (dd, J=7.8, 1.4 Hz, 1H), 3.08-3.02 (m, 4H), 1.86-1.79 (m, 2H), 1.69-1.62 (m, 2H).

1. additionUpon completion of addition
2. temperatureAfter this time, the reaction mixture was cooled to 0° C.
3. stirringThe resulting mixture was stirred at 0° C. for 30 min
4. additionCELITE® was added
5. filtrationThe mixture was filtered
6. washrinsed with DCM (100 mL)
7. dry with materialThe filtrate was dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto provide the crude product
11. custompurified by preparative HPLC (PHENOMENEX® Axia Luna 5μ C18 30×100 mm
12. custom10 min gradient
13. custom100% B and 5 min 100% B
14. extractionwas then extracted with ethyl acetate (20 mL)
15. dry with materialThe organic layer was dried over anhydrous Na2SO4
16. filtrationfiltered
17. concentrationconcentrated

ORD record

ord-7b21a736058f408f91219e63dba902ac

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062028B2