4-(Pyridin-3-yl)benzaldehyde

General procedure: The reaction vessel was charged with heteroaryl bromides (1.0mmol), arylboronic acid (1.2mmol), KTetrakis (TRIPHENYLPHOSPHINE) palladium (0. 65 g, 0. 56 MMOL), 4-FORMYLPHENYLBORIC acid (2. 81 g, 18. 7 MMOL), 2M aqueous sodium carbonate (18. 7 ml, 37. 4 mmol) and ethanol were added to the nitrogen-saturated solution of 3-bromopyridine (2. 66 g, 16. 8 mmol) in toluene and refluxed under nitrogen for 8 hrs. Water was added to the solution and extracted with ethyl acetate, washed with water and brine and dried. Solvents were removed under reduced pressure and the residue was purified by silica gel column chromatography (eluent ; hexane/ethyl acetate = 1/1. 5) to give 4- (3-PYRIDYL) benzaldehyde (0. 78 g, 25percent).General procedure: 4.3.10 Anhydrous zinc chloride (6.8 g, 0.05.0 moles) and then 3-bromopyridine (26.4 g, 0.167 mol) are added with agitation under an inert atmosphere, to a solution constituted by toluene (78 g) and tetrahydrofuran (66 g). [00117] Palladium tetrakistriphenylphosphine (0.102 g, 0.089 mmol) and then, over a period of 2 hours, a solution of the Grignard reagent of 4-bromobenzaldehyde dimethyl acetal (169.3 g of solution, equal to 0.197 mol), prepared analogously to Example 1, are added to the suspension maintained at 50° C. with agitation and under an inert atmosphere. [00118] The reaction mixture is maintained at 50° C. for 30 minutes and then cooled to 25° C. [00119] 4-(3'-pyridyl)benzaldehyde (25.6 g, 0.14 mol) is obtained with a yield of 84percent in moles relative to the 3-bromopyridine added, turnover of the catalyst (Pd): 1576. [00120] IR: 1701.6 cmExample 24 was repeated but in the absence of zinc chloride. The yield in moles of 4-(3'-pyridyl)benzaldehyde relative to the 3-bromopyridine added was 3percent, turnover of the catalyst (Pd) 56.General procedure: In an argon-filled glovebox, a 10 mL microwave vial was charged with Pd(PPh3)4 (14.35 mg, 0.0125 mmol), Cu2O (21.3 mg, 0.15 mmol), 1, 10-phenanthroline (8.95 mg, 0.05 mmol), the potassium pyridylcarboxylate (0.50 mmol), aryl bromide(0.75 mmol) and anhydrous DMA (3.0 mL). The resulting solution wasirradiated in a microwave reactor (Biotage Initiator Eight EXP) with a 2 minprestirring period, followed by 10 min at 60 C. The reaction was then heatedat 180 C for 3 h 50 min. The maximum pressure noted was 3 bar. Aftercompletion of the reaction, H2O was added to the mixture which was thenextracted with EtOAc (3 10 mL). The combined organic layers were washedwith brine (5 mL), dried over Na2SO4, filtered, and the volatiles removed invacuo. The residue was purified by column chromatography on silica gel, yielding the corresponding biaryl product.4-bromobenzaldehyde dimethyl acetal (9.5 g, 41.1 mmoles) and palladium tetrakistriphenyl phosphine (50 mg, 0.04 mmoles) were added to a mixture of anhydrous zinc chloride (2.1 g 15.4 mmoles) in anhydrous tetrahydrofuran (23 g), with stirring, in an inert atmosphere. A solution of Grignard A (40.3 g) was added over 4 hours to the resulting mixture, which was kept at 50°C with stirring, in an inert atmosphere. The reaction mixture was kept at 50°C for 30 minutes and then cooled to 20-25°C. An 85percent yield of 4- (3APOS;-PYRIDYL)- BENZALDEHYDE-DIMETHYL acetal, relative to the 4- bromobenzaldehyde dimethyl acetal loaded, was obtained. After acid hydrolysis, an 85percent yield of 4- (3APOS;-PYRIDYL)- BENZALDEHYDE was obtained.4-bromobenzaldehyde dimethyl acetal (9.5 g, 41.1 mmoles) and palladium tetrakistriphenyl phosphine (50 mg, 0.04 mmoles) were added to a mixture of anhydrous zinc chloride (2.1 g 15.4 mmoles) in anhydrous tetrahydrofuran (23 g), with stirring, in an inert atmosphere. A solution of Grignard A (40.3 g) was added over 4 hours to the resulting mixture, which was kept at 50° C. with stirring, in an inert atmosphere. The reaction mixture was kept at 50° C. for 30 minutes and then cooled to 20-25° C. An 85percent yield of 4-(3'-pyridyl)-benzaldehyde-dimethyl acetal, relative to the 4-bromobenzaldehyde dimethyl acetal loaded, was obtained. After acid hydrolysis, an 85percent yield of 4(3'-pyridyl)-benzaldehyde was obtained.[0331] Cis/trans 4-(pyridin-3-yl)phenyl-1-carbaldehyde oximes (53). To a solution of 52 (547 mg, 2.99 mmol) in 95 % ethanol (6 mL) was added hydroxylamine hydrochloride (228 mg, 3.28 mmol), sodium acetate (269 mg, 3.28 mmol) and the resultant slurry was heated to reflux and stirred for 25 min. The solvent was removed in vacuo and the residue was triturated with CH2Cl2. The white solid (TLC: CH30H/CHCl3, 5/95, Rf = 0.22) was collected by filtration to afford the cisltrans mixture of the title compound 53 (580 mg, 98% yield) as a yellow solid: mp = 160-165 C dec.; 1H NMR (DMSO-D6) 8 11. 39 (s, 1H), 8.98 (s, 1H), 8.63 (m, 1H), 8.21 (m, 2H), 7.79 (m, 2H) 7.72 (m, 2H), 7.57 (m, 1H), 7.57 (m, 1H); LRMS (ESI) nilz calcd for C12H11N2O [M + H] + 199, found 199.General procedure: To a solution of a 3- or 4-bromobenzaldehyde in a mixture DMF/water (3:1; 14.8mL/mmol) were added boronic acid derivative (1.5 equiv.), Pd(PPh3)4 (5mol%), and K2CO3 (2 equiv.). The reaction mixture was heated under microwave irradiation (130C) until TLC showed complete conversion of the starting material (0.5-1h). After cooling, the mixture was extracted with dichloromethane. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered off, and concentrated under reduced pressure to afford the corresponding crude product 2. (0027) Compounds 2a-2p were synthesized following the procedure described above from the corresponding boronic acids.General procedure: In a oven-dried flask and under nitrogen flow, benzenediazonium o-benzenedisulfonimide (1a, 161mg, 0.5mmol) was added to a suspension of 4-methoxyphenylboronic acid (3a, 91mg, 0.6mmol), [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I) (2:1) toluene adduct (39mg, 0.025mmol, 5mol%), Cs2CO3 (325mg, 1mmol) in THF (5mL). The resulting mixture was stirred at room temperature for 2h; the completion of the reaction was confirmed by the absence of azo coupling with 2-naphthol. Then, the reaction mixture was poured into diethyl ether/water (100mL, 1:1). The aqueous layer was separated and extracted with diethyl ether (50mL). The combined organic extracts were washed with water (50mL), dried with Na2SO4 and evaporated under reduced pressure. GC-MS analyses of the crude residue showed 4-methoxybiphenyl (4a), MS (EI): m/z 184 (M+) as the major product, besides traces of biphenyl, MS (EI): m/z 154 (M+), 4, 4'-dimethoxybiphenyl, MS (EI): m/z 214 (M+), N-phenyl-o-benzenedisulfonimide, MS (EI): m/z 295 (M+). The crude residue was purified on a short column, eluting with petroleum ether/diethyl ether (9:1). The only isolated product was the title compound (4a, 81mg, 88% yield).

Molecular Weight:183.21
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:183.068413911
Monoisotopic Mass:183.068413911
Topological Polar Surface Area:30
Heavy Atom Count:14
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes