4-(BENZYLOXY)PYRIDINE

A flask is charged with NaH (60percent dispersion in mineral oil, 0.72 g, 18.0 mmol) then suspended in DMF (30 mL) and cooled to 5° C. To this mixture is added benzyl alcohol (1.04 mL, 10.0 mmol) drop-wise. The mixture is stirred for 15 minutes then 4-chloropyridine-HCl (1.00 g, 6.67 mmol) is added in three portions over 5 min. The resulting mixture is stirred at 5° C. for 10 min then warmed to 60° C. and stirred for 1.5 h. The mixture is then cooled to 23° C., treated with water, and extracted with EtOAc. The combined organics are dried with MgSOExample 3 General procedure: Phenol (0.5 mmol), benzyl bromide(1.2 mmol) and KOH (2.0 mmol) was added to the DES (1 mL) and heated at temperature (80°C) for 2 h. After cooling to room temperature water was added and the product was extracted with ethyl acetate (1 3 mL) andanalyzed by GC–MS after the addition of hexamethylbenzene as an internal standard. The product was purified using column chromatography on silica gel(hexane/EtOAc::99:1). The pure product was characterized by A flask is charged with NaH (60percent dispersion in mineral oil, 0.72 g, 18.0 mmol) then suspended in DMF (30 mL) and cooled to 5° C. To this mixture is added benzyl alcohol (1.04 mL, 10.0 mmol) drop-wise. The mixture is stirred for 15 minutes then 4-chloropyridine-HCl (1.00 g, 6.67 mmol) is added in three portions over 5 min. The resulting mixture is stirred at 5° C. for 10 min then warmed to 60° C. and stirred for 1.5 h. The mixture is then cooled to 23° C., treated with water, and extracted with EtOAc. The combined organics are dried with MgSOExample 3 General procedure: Phenol (0.5 mmol), benzyl bromide(1.2 mmol) and KOH (2.0 mmol) was added to the DES (1 mL) and heated at temperature (80°C) for 2 h. After cooling to room temperature water was added and the product was extracted with ethyl acetate (1 3 mL) andanalyzed by GC–MS after the addition of hexamethylbenzene as an internal standard. The product was purified using column chromatography on silica gel(hexane/EtOAc::99:1). The pure product was characterized by Step 1 4-Benzyloxypyridine To a suspension of sodium hydride (80% dispersed in oil, 876 mg, 29.2 mmol) in DMSO (10 ml) was added benzyl alcohol (3 ml, 29.2 mmol) and the mixture stirred at room temperature for 1 hour. To this was added 4-chloropyridine (3.3 g, 29.2 mmol) and the reaction stirred at room temperature overnight. The precipitated sodium chloride was removed by filtration and the filtrate diluted with water (100 ml) and extracted with ether (3*120 ml). The combined organic layers were dried (MgSO4) and evaporated in vacuo to yield the title compound as an oil (4.8 g, 95%); deltaH (CDCl3) 5.11 (2H, s, PhCH2 O), 6.87 (2H, d, J 6.3 Hz, 3-H, 5-H), 7.29-7.42 (5H, m, Ph), and 8.42 (2H, d, J 6.3 Hz, 2-H, 6-H).General procedure: To a stirred solution of N-heteroaromatic compounds in chloroform (0.5 M) was added meta-chloroperoxybenzoic acid (m-CPBA) (2.0 eq) in portions at 0 C. After the completion of this course, the reaction mixture was allowed up to room temperature and stirred overnight. An aqueous solution of saturated K2CO3 was added to the mixture to neutralize residual m-CPBA. The resulting mixture was extracted with CHCl3 and isopropanol (volume ratio = 9:1) three times (3 x 30 mL). The organic phase were combined and washed with saturated NaCl solution (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to give crude products, which were purified by column chromatography. The new products were characterized by 1H NMR, 13C NMR and HRMS.General procedure: Phenol (0.5 mmol), benzyl bromide(1.2 mmol) and KOH (2.0 mmol) was added to the DES (1 mL) and heated at temperature (80C) for 2 h. After cooling to room temperature water was added and the product was extracted with ethyl acetate (1 3 mL) andanalyzed by GC-MS after the addition of hexamethylbenzene as an internal standard. The product was purified using column chromatography on silica gel(hexane/EtOAc::99:1). The pure product was characterized by 1H NMR and 13CNMR.Table 4 Comparison of different methodologies for benzylation of phenols with benzyl bromide

Molecular Weight:185.22
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:185.084063974
Monoisotopic Mass:185.084063974
Topological Polar Surface Area:22.1
Heavy Atom Count:14
Complexity:148
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes