Ammonium Chloride → Methyl 3-(2-amino-4-fluorophenylamino)-2-methylpropanoate

To a solution of methyl 3-(4-fluoro-2-nitrophenylamino)-2-methylpropanoate (14.0 g, 54.6 mmol) in ethanol (250 mL) were added zinc powder (14.2 g, 218 mmol) and saturated ammonium chloride (28.4 mL) at 0° C. Once addition was completed, the reaction mixture was stirred at reflux for 1 hour. Then the mixture was cooled to room temperature, filtered, and washed with ethanol (200 mL). The organic phase was concentrated in vacuo, dissolved in water (250 mL), and extracted with ethyl acetate (200 mL*3). The combined organic layers was separated, dried over anhydrous sodium sulfate, and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1) to afford methyl 3-(2-amino-4-fluorophenylamino)-2-methylpropanoate as a black solid (10.0 g, 81%).

1. additionOnce addition
2. temperatureat reflux for 1 hour
3. filtrationfiltered
4. washwashed with ethanol (200 mL)
5. concentrationThe organic phase was concentrated in vacuo
6. dissolutiondissolved in water (250 mL)
7. extractionextracted with ethyl acetate (200 mL*3)
8. customThe combined organic layers was separated
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated
11. customto give a residue
12. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1)

ORD record

ord-7ecca4a3beff4a488eef176959f172b2

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422292B2