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3-Amino-2-fluorobenzonitrile is a derivative of fluorobenzonitrile. This compound is used as a pharmaceutical intermediate in pharmaceutical synthesis and scientific research.

Step 1: To a round-bottomed flask under nitrogen protection were added 1 eq. of 3-chloro-2-fluoroaniline (3A), 1.5 M of 1-methyl-2-pyrrolidinone (NMP, as 3A), 2.2 eq. of sodium cyanide, and 1.35 eq. of nickel (II) bromide. The concentration of the reaction solution was diluted to half of the original concentration by supplementing with NMP, slowly warmed to 200 ± 5 °C and the reaction was stirred for 4 days under nitrogen atmosphere. After completion of the reaction, the mixture was cooled to room temperature. The reaction mixture was diluted with 30 times volume of tert-butyl methyl ether (MTBE) and filtered through diatomaceous earth. The diatomaceous earth pad was subsequently washed with 10 times volume of MTBE. The organic phase was washed sequentially with 40x volume of brine, 2 x 40x volume of water and 40x volume of brine. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to give a brown solid. The solid was dried at 40 °C under vacuum at -30 inches Hg for 8 hours to give the target compound 3B in 71% yield.

[1] Patent: US2006/14761, 2006, A1. Location in patent: Page/Page column 32
[2] Patent: WO2007/75377, 2007, A2. Location in patent: Page/Page column 58
[3] Patent: WO2007/70626, 2007, A2. Location in patent: Page/Page column 45
[4] Patent: WO2007/70683, 2007, A2. Location in patent: Page/Page column 88
[5] Patent: WO2007/78839, 2007, A2. Location in patent: Page/Page column 46