5-Chloro-2-methoxybenzonitrile

Ethyl 5-chloro-2-methoxybenzimidate hydrochloride A cooled solution of Example 128C; Ethyl 5-chloro-2-methoxybenzimidate hydrochloride; A cooled solution of Example 128C; Ethyl 5-chloro-2-methoxybenzimidate hydrochloride; A cooled solution of To a glass lined reactor were charged potassium tert-butoxide (1.5 Kg/Kg, 2.4 equiv) and THF (12.2 Kg/Kg) at 0 C. A mixture of compound 4 (1.0 Kg), N-Methyl-N- formylhydrazine (1.0 Kg/Kg, 2.30 equiv) and THF (5.3 Kg/Kg, 6.0 L/Kg) was added slowly. The reactor line was rinsed with THF (0.5 Kg/Kg). The reaction crude was aged at 0 C until reaction reached completion. Water (5.0 Kg/Kg) was added, and the resulting mixture was aged at 0 C for 30 min, heated to 40 C and aged for additional 30 min. The layers were separated and the aq layer discarded. The organic layer was washed with brine (15 wt%, 5.7 Kg/Kg) before distilling under vacuum until total volume became approximately 5 L/Kg. Four put/take distillations with ethyl acetate (4 x 10 L/Kg) were undertaken for the purpose of azeotropic drying. The crude was cooled to 20 C. Sulfuric acid (0.66 Kg/Kg, 1.10 equiv) was added, and the slurry was agitated for 2-3 h. Product was isolated by filtration. The cake was consecutively washed with ethyl acetate (2 chi 6.5 L/Kg) and heptane (8 L/Kg), and dried under vacuum at 45 C. Compound 5 was isolated in 99 AP and 83% yield.To a glass lined reactor were charged potassium tert-butoxide (1.5 kg/kg, 2.4 equiv) and THF (12.2 kg/kg) at 0 C. A mixture of Compound 4 (1.0 kg), L-methyl-N- formyl hydrazine (1.0 kg/kg, 2.30 equiv) and THF (5.3 kg/kg, 6.0 L/kg) was added slowly. The reactor line was r sed with THF (0.5 kg/kg). The reaction crude was aged at 0 C until reaction reached completion. Water (5.0 kg/kg) was added, and the resulting mixture was aged at 0 C for 30 min, heated to 40 C and aged for additional 30 min. The layers were separated and the aqueous layer was discarded. The organic layer was washed with brine (15 wt%, 5.7 kg/kg) before distilling under vacuum until total volume became approximately 5 L/kg. Four put/take distillations with ethyl acetate (4 x 10 L/kg) were undertaken for the purpose of azeotropic drying. The crude was cooled to 20 C. Sulfuric acid (0.66 kg/kg, 1.10 equiv.) was added, and the slurry was agitated for 2-3 h. Product was isolated by filtration. The cake was consecutively washed with ethyl acetate (2 c 6.5 L/kg) and heptane (8 L/kg), and dried under vacuum at 45 C. Compound 5 was isolated in 99 AP and 83% yield.General procedure: 2-Ethylbenzonitrile (7.6mmol) and KOH (24.8mmol) were suspended in ethane-1, 2-diol (10mL) and stirred at 170C for 7h. Then, the reaction mixture was cooled down to rt, H2O (50mL) was added and the resulting mixture was extracted three times with ether (30mL). pH of the aqueous layer was adjusted to 1 by diluted HCl and the aqueous phase was extracted three times with ether (40mL). Organic phases were collected, extracted three times with H2O (40mL) and dried over Na2SO4. The solvent was removed and obtained compound was directly used in the next step. Yield: 89.0%, white solid; mp: 64-65C; IR: 3400-2300 (b, OH), 2977 (as CH3), 2955 (as CH2), 2869 (s CH3), 1681 ( CO), 1601, 1575, 1488, 1447 ( CC aromatic) cm-1; 1H NMR (DMSO-d6, 300MHz): delta 12.79 (1H, br s, COOH), 7.76 (1H, d, J=7.0Hz), 7.43 (1H, t, J=7.5Hz), 7.33-7.21 (2H, m), 2.90 (2H, q, J=7.4Hz, CH2), 1.14 (3H, t, J=7.4Hz, CH3); 13C NMR (DMSO-d6, 75MHz): delta 169.14, 145.12, 131.96, 130.54, 130.35, 130.34, 126.04, 27.03, 16.32.General procedure: A mixture of aryl halide (1.0 mmol), phenylboronic acid (1.2 mmol), K2CO3 (2.0 mmol), novel ligand (0.1 mol %, 0.5 mg), and Pd(OAc)2 (0.1 mol%, 0.23 mg) was heated in water (5 ml) at 80 C temperature. The progress of the reaction is monitor by TLC. After the completion of the reaction, ethyl acetate (10 ml) was added to the reaction mixture and extracted with ethyl acetate (3 x 10 ml). The combined organic layer was dried with anhyd. Na2SO4 and the solvent were concentrated in vacuum to obtain a light yellow-white solid. The residue was purified by silica gel column chromatography (5-10% EtOAc in hexane) to afford the corresponding pure products.

Molecular Weight:167.59
XLogP3:2.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:167.0137915
Monoisotopic Mass:167.0137915
Topological Polar Surface Area:33
Heavy Atom Count:11
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes