Trifluoroacetic acid → HCID 22557236, compound

To a solution of 1-bromo-2-(3,3-diethoxypropoxy)-3-nitrobenzene (500 mg, 1.436 mmol) in AcOH (5.0 mL) was added zinc (939 mg, 14.36 mmol) and the mixture was stirred at room temperature for 90 min. After this time, the reaction mixture was filtered and the filtrate was concentrated. The resulting residue was dissolved in DCM (5 mL) and treated with TFA (5 mL) and triethylsilane (1.147 mL, 7.18 mmol). The resulting mixture was stirred at room temperature for 1 h and then concentrated. The resulting residue was 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 (181 mg, 53% yield). LCMS, [M+Na]+=228.0. 1H NMR (400 MHz, CDCl3) δ 7.01 (dd, J=7.8, 1.6 Hz, 1H), 6.68 (t, J=7.9 Hz, 1H), 6.62 (dd, J=7.9, 1.6 Hz, 1H), 4.20-4.13 (m, 2H), 3.31-3.22 (m, 2H), 2.08-1.98 (m, 2H).

1. filtrationAfter this time, the reaction mixture was filtered
2. concentrationthe filtrate was concentrated
3. dissolutionThe resulting residue was dissolved in DCM (5 mL)
4. stirringThe resulting mixture was stirred at room temperature for 1 h
5. concentrationconcentrated
6. customThe resulting residue was purified by preparative HPLC (PHENOMENEX® Axia Luna, 5μ
7. custom10 min gradient
8. custom100% B and 5 min 100% B
9. extractionwas then extracted with ethyl acetate (20 mL)
10. dry with materialThe organic layer was dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-2937f9654b9242099e54b890786c9a40

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062028B2