2-Amino-4-methoxybenzonitrile

Intermediate 3 : 2-Iodo-4-methoxybenzonitrile; To a solution of 4-methoxy-2-nitrobenzonitrle (5.00 g, 22.46 mmol) in EtOH (93 mL) was added 5percent Pd-C (0.500 g) under nitrogen atmosphere. The resulting mixture was hydrogenated at 1 atm. After stirring for 1 O h, the mixture was filtered through celite, washed with EtOAc/MeOH. The combined filtrates were concentrated in vacuo and the residue was purified by column chromatograph on SiOIntermediate 3 : 2-Iodo-4-methoxybenzonitrile; To a solution of 4-methoxy-2-nitrobenzonitrle (5.00 g, 22.46 mmol) in EtOH (93 mL) was added 5% Pd-C (0.500 g) under nitrogen atmosphere. The resulting mixture was hydrogenated at 1 atm. After stirring for 1 O h, the mixture was filtered through celite, washed with EtOAc/MeOH. The combined filtrates were concentrated in vacuo and the residue was purified by column chromatograph on SiO2 using 80 to 100 % gradient of EtOAc in hexanes to afford 4-methoxy-2-amiobenzonitrle (3.23 g, 99%). 4-Methoxy-2-aminobenzonitrle (1.0 g, 6.58 mmol) was dissolved in a mixture of H2O (7 niL), acetic acid (7 niL), and cone. HCl at rt, followed by addition of a solution Of NaNO2 (0.513 g, 7.43 mmol) in H2O (2 niL) at 0 0C for 5 min. To the above mixture KI (2.18 g, 13.2 mmol) was added and after stirring for 10 h at rt, the resulting mixture was treated with solid NaHSO3 and diluted with water. The product portion was extracted with CH2Cl2, washed with satd. NaHCO3, brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography on SiO2 using 10 to 50% gradient of EtOAc in hexane to provide the example intermediate (1.0 g, 59%).General procedure: A suspension of the appropriate 2-aminobenzonitrile 6a-d(10 mmol), appropriate alkyl or benzyl bromoacetate (10 mmol) andNaHCO3 (0.99 g, 12 mmol, 1.2 equiv.) in the appropriate solvent(10 mL) was stirred at reflux for 24 h. After this time, the appropriatealkyl or benzyl bromoacetate (10 mmol) was added and the mixtureheated at reflux for an additional 24 h. The reaction mixture was cooledto ambient temperature and filtered through Celite, then the filtrate wasevaporated in vacuo. The residue was diluted with dichloromethane(25 mL) and washed sequentially with water (10 mL) and brine(10 mL). The organic layer was dried over Na2SO4, filtered and concentratedunder reduced pressure, and the residue was stirred with theappropriate solvent or purified by flash column chromatography onsilica gel.

Molecular Weight:148.16
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:148.063662883
Monoisotopic Mass:148.063662883
Topological Polar Surface Area:59
Heavy Atom Count:11
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes