Methyl 3-(bromomethyl)benzoate

30mL CClA solution of methyl 3-methylbenzoate (47 g, 0.31 mol) in CCl4 (200 mL) was heated to reflux followed by addition of AIBN (2.6 g) in one portion. After that, NBS (67 g, 0.38 mol) was added carefully to the mixture during 2 h, and then the reaction was refluxed for an additional 5 h. After cooling to r.t. the mixture was filtered and evaporated under vacuum to give methyl 3-(bromomethyl)benzoate (10, 67 g, Yield: 94percent) as a yellowish oil. The obtained oil was then dissolved in triethyl phosphate (130 g, 0.71 mol), heated to 160 °C and kept at this temperature for an additional 10 h. The mixture was concentrated on a rotary evaporator and then purified by flash chromatography(PE:EA = 5:1~PE:EA = 1:3) to give 11 as a yellow oil, which was used without any further purification.To a solution of methyl 3-methylbenzoate (4.0 g, 26.60 mmol) in CCU (150 mL) was added BS (5.69 g, 31.96 mmol), and the suspension was heated at 80 °C for 5 min and AIBN (2.18 g, 13.30 mmol) was added. The suspension continued to stir at 80 °C for 16 h. The mixture was cooled to RT and filtered. The filtrate was concentrated to give the crude product, which was purified by silica gel chromatography eluting with EA/petroleum ether from 0percent to 3percent to give methyl 3-(bromomethyl)benzoate (5.7 g, 94percent) as a white oilTo a mixture of methyl-m-toluate (180 g, 1.2 mol) and N-bromosuccimide (235 g, 1.32 mol) in CCl4 (2 L) was added in portion benzoyl peroxide (18 g, 0.1 times) at 50° C. The mixture was refluxed for 5 h. Then the mixture was allowed to cool down to 40° C. and the solid was filtered off. The filtrate was concentrated to give methyl 3-(bromomethyl)benzoate (252 g, 91percent) as light yellow liquid.To a solution of Intermediate BL (5.0g, 33.29 mmol) and benzoyl peroxide (0.4 g, 1.66 mmol) in CC1Synthesis Synthesis of Compound 22; Methyl-3-methyl benzoate (1.5 g, 10 mmol) and N-bromosuccinimide (5.34 g, 30 mmol) was suspended in cyclohexane (50 ml). To the suspension, a catalytic amount of hydrogen peroxide was added, and the reaction mixture was heated to reflux for 16 h. The reaction mixture was then filtered, and evaporated to yield 0.231 g (10percent) as a yellow oil. Compound 21 was then formed by coupling methyl 3-bromomethylbenzoate to thionicotinamide intermediate IIa in the manner of Method A to yield 180 mg (45percent) of compound 22 as a crystalline material. ESI-MS m/z=397.1 [M+H]Methyl-3-methyl benzoate (1.5 g, 10 mmol) and N-bromosuccinimide (5.34 g, 30 mmol) was suspended incyclohexane (50 ml). To the suspension, a catalytic amount of hydrogen peroxide was added, and the reaction mixturewas heated to reflux for 16 h. The reaction mixture was then filtered, and evaporated to yield 0.231 g (10percent) as a yellowoil. Compound 21 was then formed by coupling methyl 3-bromomethylbenzoate to thionicotinamide intermediate IIa inthe manner of Method A to yield 180 mg (45percent) of compound 22 as a crystalline material. ESI-MS m/z = 397.1 [M+H]+.To the solution of compound B4 (28 g, 0.168 mol) in 700 mL of EtSynthesis of Compound B5: [Show Image] To the solution of compound B4 (28 g, 0.168 mol) in 700 mL of EtPreparation of Methyl 3-bromomethylbenzoate; To a solution of Methyl 3-methylbenzoate (150 g, I mol) and l, 3-Dibromo-5, 5-dimethyl hydantoin (DDH) (15O g, 0.52 mol) in dichloromethane (500 ml) was added AIBN (0.1 g, 0.0006 mol) at room temperature and heated under reflux for 1O h. AIBN in 0.1 g lots were added intermittently during reflux to complete the reaction. After completion of the reaction (monitored by TLC), the reaction mixture was poured into cold water (600 ml) and the organic layer was separated. The aqueous layer was extracted again with dichloromethane (200 ml). The combined organic layer was washed with water and dried over anhydrous sodium sulphate and the solvent was removed by distillation. Colorless liquid, 220 g (96 percent yield)Note: The product contains some dibromo derivative also. Benzoyl peroxide could be used as a radical initiator.Reference To a solution of 3-Bromomethyl-benzoic acid (1 g, 4.6 mmol) in methanol (20 mL) was added thionyl chloride (1.1 g, 9.3 mmol) drop wise at 25 °C. The reaction mixture was refluxed over a period of 1 h and methanol was removed under reduced pressure to obtain crude sticky mass. The crude mass was diluted with ethyl acetate and washed with water and dried over sodium sulphate. Ethyl acetate was evaporated under reduced pressure to obtain 3-Bromomethyl-benzoic acid methyl ester as light yellow oil (1.0 g, 94.0 percent)To a solution of 3-Bromomethyl-benzoic acid (1 g, 4.6 mmol) in methanol (20 mL) was added thionyl chloride (1.1 g, 9.3 mmol) drop wise at 25° C.

Molecular Weight:229.07
XLogP3:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes