Methyl 2-bromo-5-methylbenzoate

To a suspension of compound 4 (2.15 g, 10 mmol) in dry DCM (40 mL) and DMF (0.2 mL) at 0 °C was slowly added oxalyl chloride (1.3 mL, 15 mmol). After being stirred for 1 h at room temperature, the reaction mixture was treated with MeOH (20 mL) and then stirred for 3 h. The resulting solution was neutralized with saturated aqueous NaThe 2-bromo-5-methyl benzoic acid (10.75g, 50mmol) is added to 500 ml round bottom flask, with methanol (100 ml) to dissolve fully, and then slowly adding concentrated sulfuric acid (1.5 ml, 25mmol), reaction solution gradually heated up to reflow, reaction 16 hours. Stop reaction, to be reacted after cooling to room temperature, solvent evaporating under reduced pressure, the residue is dissolved in dichloromethane (200 ml) is dissolved, and with water (200 ml) and saturated salt water (100 ml) washing, separating the organic layer, drying with anhydrous sodium sulfate. Filtering, the filtrate concentrated under reduced pressure, the resulting residue is purified by silica gel column chromatography separation ((v/v)=200/1 petroleum ether/ethyl acetate) to obtain the title compound as a yellow oily matter (11.00g, 96.1percent).Acetyl chloride (1.66 ml, 23.3 mmol) was added to a stirred solution of 2-bromo-5- methylbenzoic acid (2.00 g, 9.30 mmol) in MeOH (50 ml) at 0°C. The reaction was then stirred at r.t. over night. More acetyl chloride (1 ml, 14.0 mmol) was added and the reaction was stirred for 24 hours. The solvent was removed in vacuo and the crude material was dissolved in Et0Acetyl chloride (1.66 ml, 23.3 mmol) was added to a stirred solution of 2-bromo-5- methylbenzoic acid (2.00 g, 9.30 mmol) in MeOH (50 ml) at 0°C. The reaction was then stirred at r.t. over night. More acetyl chloride (1 ml, 14.0 mmol) was added and the reaction was stirred for 24 hours. The solvent was removed in vacuo and the crude material was dissolved in Et0Step 1: Dimethyl sulfate (2.2 mL, 21.1 mmol)was slowly dropped under stirring into a solution of 2-bromo-5-methylbenzoic acid (3.78 g, 17.6 mmol) in 22mLmethanolic NaOH. Themixturewas refluxed for 30min.After cooling, waterwas added and the solutionwas 3×extracted with diethyl ether. The combined extractswere washed twice with 5percent aq NaHCO3 solution then with satd. NaCl solution and finallywith H2O. After drying over Na2SO4, the solvent was removed and the residue was purifiedby CC (Kieselgel, CH2Cl2). Yield: 2.4 g (10.5 mmol, 60percent) light-yellow liquid. IR: ν =2952, 1736 (C O), 1435, 1300, 1252, 1205, 1030. 1H NMR (in agreement with lit.11): δ= 2.33 (s, 3H, CH3), 3.92 (s, 3H, OCH3), 7.13 (dd, 1H, J = 2.0 Hz/8.0 Hz, 4-H), 7.52 (d, 1H, J = 8.0 Hz, 3-H), 7.59 (d, 1 H, J = 2.0 Hz, 6-H). 13C NMR (in agreement with lit.11):δ = 20.74 (OCH3), 52.40 (ArCH3), 118.23 (Cq, ar), 131.81, 131.87, 133.42, 134.06 (CHar), 137.25 (Cq, ar), 166.29 (C O). MS: m/z (percent) = 230 (37) [M]+, 228 (38) [M]+, 199(94) [M– OCH3]+, 197 (100) [M – OMe]+, 171 (23) [M – CO2CH3]+, 169 (25) [M – CO2CH3]+, 91 (14) [C7H7]+, 90 (48), 89 (34), 63 (15). C9H9BrO2 (229.08): calcd. C 47.19, H 3.96, Br34.88, found C 47.01, H 3.97, Br 34.85.In a 250 mL single-mouth flask, 5.00 g (23.26 mmol) of Compound 1 and 6.64 g (28.99 mmol) of Compound 2 were added, 150 mL of methanol was added, and the water separator was installed and refluxed at 70° for 24 hours to stop the reaction. After spin-drying the solvent, the reaction was washed with water several times and extracted with ethyl acetate. The ethyl acetate layer was purified by rotary column chromatography to obtain 5.5 g of compound 2 as an oil

Molecular Weight:229.07
XLogP3:2.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:170
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes