2-Amino-2-methyl-1-propanol → 2-amino-6-(2-amino-2-methylpropoxy)benzonitrile

Temperature

0 °C

To a solution of 2-amino-2-methylpropan-1-ol (14.4 g, 161 mmol) in anhydrous THF (150 mL) was added NaH (6.8 g, 161 mmol, 60% in mineral oil) in small portions at 0° C. under nitrogen. The mixture was stirred at 0° C. for 30 minutes and then stirred at room temperature for another 30 minutes. The solution was cooled down to 0° C. again, and to this solution was added dropwise a solution of 2-amino-6-fluorobenzonitrile (20.0 g, 147 mmol) in anhydrous THF (50 mL). The reaction mixture was then refluxed overnight under nitrogen. The reaction mixture was cooled down to room temperature and carefully quenched with aqueous NH4Cl solution and extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude mixture was purified by chromatography on silica gel eluting with 10% MeOH in DCM to give the title compound as yellow solid (23.4 g 71%). 1H NMR (400 MHz, DMSO-d6) δ 1.08 (s, 6H), 3.15 (s, 2H), 3.64 (s, 2H), 5.98 (s, 2H), 6.13 (d, J=8.0 Hz, 1H), 6.31 (d, J=8.4 Hz, 1H), 7.15 (t, J=8.4 Hz, 1H). MS 236 (MH+).

1. stirringstirred at room temperature for another 30 minutes
2. temperatureThe solution was cooled down to 0° C. again
3. temperatureThe reaction mixture was then refluxed overnight under nitrogen
4. temperatureThe reaction mixture was cooled down to room temperature
5. customcarefully quenched with aqueous NH4Cl solution
6. extractionextracted with ethyl acetate (3×)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude mixture was purified by chromatography on silica gel eluting with 10% MeOH in DCM

ORD record

ord-57466c3b2a3945b3b43e624e862bd99c

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815956B2