Toluene → 7-Bromo-2,3-dihydro-N-phenyl-1h-inden-1-amine

Temperature

90 °C

To a stirred solution of 10.4 g (112 mmol) of aniline in 60 ml of toluene 5.31 g (28.0 mmol) of TiCl4 was added for 30 min at room temperature in argon atmosphere. The resulting mixture was stirred at 90° C. for 30 min followed by an addition of 6.00 g (28.0 mmol) of 7-bromoindan-1-one. The resulting mixture was stirred for 10 min at 90° C., poured into 500 ml of water, and crude product was extracted with 3×100 ml of ethyl acetate. The organic layer was separated, dried over Na2SO4, and then evaporated to dryness. The residue was crystallized from 10 ml of ethyl acetate at −30° C. The resulting solid was separated and dried in vacuum. After that it was dissolved in 100 ml of methanol, 2.70 g (42.9 mmol) of NaBH3CN and 0.5 ml of glacial acetic acid was added. The resulting mixture was refluxed for 3 h in argon atmosphere. The resulting mixture was cooled to room temperature and then evaporated to dryness. The residue was diluted with 200 ml of water, and crude product was extracted with 3×50 ml of ethyl acetate. The combined organic extract was dried over Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate-triethylamine=100:10:1, vol.). Yield 5.50 g (68%) of a yellow oil. Anal. calc. for C15H14BrN: C, 62.52; H, 4.90; N, 4.86. Found: C, 62.37; H, 5.05; N, 4.62. 1H NMR (CDCl3): δ 7.38 (m, 1H, 6-H in indane); 7.22 (m, 3H, 3,5-H in phenyl and 4-H in indane); 7.15 (m, 1H, 5-H in indane); 6.75 (m, 1H, 4-H in indane); 6.69 (m, 2H, 2,6-H in phenyl); 4.94 (m, 1H, 1-H in indane); 3.82 (br.s, 1H, NH); 3.17-3.26 (m, 1H, 3- or 3′-H in indane); 2.92-2.99 (m, 2H, 3′- or 3-H in indane); 2.22-2.37 (m, 2H, 2,2′-H in indane).

1. stirringThe resulting mixture was stirred for 10 min at 90° C.
2. extractionwas extracted with 3×100 ml of ethyl acetate
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. customevaporated to dryness
6. customThe residue was crystallized from 10 ml of ethyl acetate at −30° C
7. customThe resulting solid was separated
8. customdried in vacuum
9. dissolutionAfter that it was dissolved in 100 ml of methanol
10. temperatureThe resulting mixture was refluxed for 3 h in argon atmosphere
11. temperatureThe resulting mixture was cooled to room temperature
12. customevaporated to dryness
13. additionThe residue was diluted with 200 ml of water, and crude product
14. extractionwas extracted with 3×50 ml of ethyl acetate
15. extractionThe combined organic extract
16. dry with materialwas dried over Na2SO4
17. customevaporated to dryness
18. customThe residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate-triethylamine=100:10:1, vol.)

ORD record

ord-3aefdc787b164ef082de66203a9f778c

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290519B2