Sodium Hydroxide → 4-(4-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine

Temperature

110 °C

Into a 100 ml round bottomed flask with 4-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (2.28 g, 5.93 mmol), tetrabutylammonium iodide (0.110 g, 0.297 mmol) was added 6N sodium hydroxide (14.84 ml, 89 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (1.480 ml, 11.87 mmol). The reaction was heated to 110° C. for 2 h, cooled to room temperature and the mixture was extracted with EtOAc. The combined organic phase was washed with Brine (20 mL) and concentrated. The residue was purified on a silica gel cartridge and eluted with a gradient of 0% ethyl acetate/hexanes to 80% over 10 column volumes. The appropriate fractions were collected and evaporated to yield 4-(4-bromo-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (508 mg, 1.118 mmol, 18.84% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.40 (s, 3H) 3.00-3.09 (m, 4H) 3.76-3.81 (m, 4H) 5.26 (s, 2H) 6.54 (d, J=2.02 Hz, 1H) 6.85 (d, J=7.58 Hz, 1H) 7.13-7.21 (m, 2H) 7.57 (d, J=7.83 Hz, 1H) 7.68 (s, 1H); LC/MS: MS (ES+) m/e 455 [M+H]+.

1. temperaturecooled to room temperature
2. extractionthe mixture was extracted with EtOAc
3. washThe combined organic phase was washed with Brine (20 mL)
4. concentrationconcentrated
5. customThe residue was purified on a silica gel cartridge
6. washeluted with a gradient of 0% ethyl acetate/hexanes to 80% over 10 column volumes
7. customThe appropriate fractions were collected
8. customevaporated

ORD record

ord-e4beef904f4042d582798df18eda81d1

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778937B2