2-Fluoro-5-methylbenzonitrile

General procedure: 1800 muL (90%) Tris buffer (50 mM, pH 7.6) and 200 muL(10%) of methanol or acetone. In a 2 mL Eppendorf, NHase (10 mg) was added followed by Trisbuffer. Nitrile substrate (10 mg dissolved in 200 muL methanol or acetone) was added to the 2 mLEppendorf tube. (If an amine group was present on the nitrile substrate a Tris buffer of pH 9 wasused). The reaction mixture was incubated at 30 C on an ESCO Provocell microplateshaker/incubator (Esco Technologies, Halfway House, South Africa) (199 rpm). The reaction wasallowed to proceed for 24 h, 48 h or 5 d, depending on conversion, as monitored by TLC analysis.Ethyl acetate and water were added to the reaction mixture, and after separation, the organic layerwas concentrated under reduced pressure, and the resulting mixture was then purified by silica gelcolumn chromatography eluting with 20% to 90% ethyl acetate/ hexane.xxv) 5-Methylbenzo[d]isoxazol-3-amine I60 To a solution of acetohydroxamic acid (8.33 g, 0.11 mol) in DMF (200 ml.) was added t-BuOK (12.5 g, 0.11 mol) and the mixture was stirred at RT for 1 hour. 2-Fluoro-5-methylbenzonitrile (5 g, 0.37 mol) was then added and the mixture was heated at 60 C overnight. The mixture was diluted with water and extracted with EtOAc. The organic extract was concentrated under reduced pressure and the residue was purified by a silica gel chromatography (DCM/MeOH = 200/1 to 50/1) to give the title compound (3.0 g, 55%) as a white solid. LCMS-D: Rt 1.75 min, m/z 149.0 [M+H]+.A mixture of 16.1 (22 mg, 0, 163 mmol), thiol 13.2 (28.6 mg, 0.171 mmol) and K2C03 (56, 2 mg, 0.407 mmol) in DMF (0.65 mL) is stirred at room temperature for 7 h. The mixture is diluted with EtOAc (50 mL) and the solution is washed with water and brine, then dried (Na2S04), filtered and concentrated under reduced pressure. The residue is purified by flash chromatography (10- 20%EtOAc: Hex) to give compound 1118; MS: m/z = 283.1 (MH+); 1 H N MR (400 MHz, DMSO- cfe) delta ppm 2.44 (s, 3 H), 7.06 (tt, J=7.40, 1 .17 Hz, 1 H), 7.19 (s, 2 H), 7.31 (dd, J=8.61 , 7.43 Hz, 1 H), 7.35 (dd, J=8.22, 1 .17 Hz, 1 H), 7.69 (dd, J=8.80, 0.98 Hz, 2 H), 7.76 (d, J=8.22 Hz, 1 H), 7.91 (s, 1 H), 9.29 (s, 1 H).

2-Fluoro-5-methylbenzonitrile is used in the synthesis of indazoles which have the potential to be selective for the α2-adrenoceptor and central and peripheral nervous systems.

Molecular Weight:135.14
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Exact Mass:135.048427358
Monoisotopic Mass:135.048427358
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes