Acetic Acid → N-benzyl-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine

To a solution of 5-methoxy-2-tetralone (30 g, 170.24 mmol) dissolved in CH2Cl2 (250 mL) were added benzylamine (23 mL, 212.80 mmol) and AcOH (0.97 mL, 17.02 mmol), and the mixture was stirred for 4 h at room temperature. It was then cooled to 0° C. and NaB(OAc)3H (0.38 eq, 13.71 g, 64.69 mmol) was added over a period of 20 min. After 1 h stirring at 0° C., NaB(OAc)3H (1.07 eq, 38.61 g, 182.16 mmol) was added over a period of 30 min. It was added CH2Cl2 (100 mL), the reaction mixture warmed to room temperature and stirred for 15 h. The mixture was cooled again to 0° C., and H2O (200 mL) was added slowly. The pH of the solution was adjusted to 8.0 by adding NaHCO3 saturated aqueous solution (300 mL), and the mixture was stirred at 0° C. for 15 min. The layers were separated, and the aqueous phase was extracted with CH2Cl2 (2×150 mL). All organic phases were combined, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue (58.7 g) was purified by flash chromatography on silica gel (40:60:1-100:0:1 AcOEt/Hexane/Et3N), followed by trituration with hexane, affording 33.87 g of the title compound (Rf=0.5 (10% MeOH/CH2Cl2), yellow solid, 74% yield).

1. temperatureIt was then cooled to 0° C.
2. stirringAfter 1 h stirring at 0° C.
3. temperaturethe reaction mixture warmed to room temperature
4. stirringstirred for 15 h
5. temperatureThe mixture was cooled again to 0° C.
6. stirringthe mixture was stirred at 0° C. for 15 min
7. customThe layers were separated
8. extractionthe aqueous phase was extracted with CH2Cl2 (2×150 mL)
9. dry with materialdried over anhydrous Na2SO4
10. concentrationconcentrated in vacuo
11. customThe residue (58.7 g) was purified by flash chromatography on silica gel (40:60:1-100:0:1 AcOEt/Hexane/Et3N)

ORD record

ord-c44a70fab76a4ec48021c37129aec9e9

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08097641B2