Acetyl chloride → N-(4-Bromo-5,6,7,8-tetrahydronaphthalen-1-yl)-acetamide

To a solution of 5,6,7,8-tetrahydronaphthalen-1-amine (1 g, 6.8 mmol), triethylamine (1.9 mL, 13.6 mmol) in DCM (50 mL), is added acetyl chloride (587 mg, 7.5 mmol) dropwise. The mixture is stirred at room temperature for 2 hr. Then the mixture is concentrated and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer is separated, washed with brine and dried over sodium sulfate. After concentration, the obtained N-(5,6,7,8-tetrahydronaphthalen-1-yl)acetamide (200 mg) is dissolved in acetic acid (30 mL). To this solution is added bromine (170 mg, 1.06 mmol) dropwise. The mixture is heated at 50° C. overnight. The reaction is quenched by adding sodium sulfite aqueous solution. The mixture is extracted with ethyl acetate (3×20 mL). The organic extracts are combined and washed with sodium bicarbonate aqueous solution, brine, and dried over sodium sulfate. After concentration, the crude N-(4-bromo-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide is obtained as brown solid. The solid obtained is dissolved in methanol (5 mL) and concentrated HCl (15 mL). The mixture is refluxed at 95° C. overnight. After cooling to room temperature, the mixture is poured into ice water, and basified to pH=12 with conc. NaOH aqueous solution. Then the mixture is extracted with ethyl acetate (3×20 mL). The combined organic layer is dried over Na2SO4 and concentrated. The crude product is purified with silica gel chromatography (15% ethyl acetate in hexanes) to give 4-bromo-5,6,7,8-tetrahydronaphthalen-1-amine as beige solid. ESMS m/z 226 (M+H+).

1. concentrationThen the mixture is concentrated
2. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride
3. customThe organic layer is separated
4. washwashed with brine
5. dry with materialdried over sodium sulfate
6. concentrationAfter concentration
7. dissolutionthe obtained N-(5,6,7,8-tetrahydronaphthalen-1-yl)acetamide (200 mg) is dissolved in acetic acid (30 mL)
8. temperatureThe mixture is heated at 50° C. overnight
9. customThe reaction is quenched
10. additionby adding sodium sulfite aqueous solution
11. extractionThe mixture is extracted with ethyl acetate (3×20 mL)
12. washwashed with sodium bicarbonate aqueous solution, brine
13. dry with materialdried over sodium sulfate
14. concentrationAfter concentration

ORD record

ord-c3533b058b044112937e8e2f328b1344

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08440681B2