2,6-Dibromo-4-fluoro-3-methylbenzonitrile → (2,6-Dibromo-4-fluoro-3-methylphenyl)methanamine

Temperature

60 °C

To a stirred solution of 2,6-dibromo-4-fluoro-3-methylbenzonitrile (1.145 g, 3.91 mmol) in THF (7 mL) was added 2M borane-methylsulfide complex (8 mL, 16.00 mmol) over 5 min at room temperature. After 30 min, the reaction mixture was warmed to 60° C. and stirred for an additional 1.6 h. The mixture was cooled then quenched by the careful addition of methanol (10 mL) and 4M HCl/dioxane (2 mL). After 30 min, the reaction mixture was heated to 50° C. for 45 min and concentrated. The residue was taken up in sat. Na2CO3 (20 mL) and extracted with CH2Cl2 (3×25 mL). The combined CH2Cl2 extracts were washed with water (20 mL) followed by brine (20 mL), then dried (Na2SO4), filtered and concentrated to afford (2,6-dibromo-4-fluoro-3-methylphenyl)methanamine (1.16 g, 3.91 mmol, 100% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ: 7.31 (1 H, d, J=8.9 Hz), 4.19 (2 H, s), 2.34 (3 H, d, J=2.4 Hz), 1.59 (2 H, brs). LCMS (M+H) calcd for C15H21N2O3: 297.91; found: 297.85.

1. temperatureThe mixture was cooled
2. customthen quenched by the careful addition of methanol (10 mL) and 4M HCl/dioxane (2 mL)
3. waitAfter 30 min
4. temperaturethe reaction mixture was heated to 50° C. for 45 min
5. concentrationconcentrated
6. extractionextracted with CH2Cl2 (3×25 mL)
7. washThe combined CH2Cl2 extracts were washed with water (20 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-593dbe42dc52472ca443a4b5d1135de6

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2