Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:3]=1[C:4]([OH:6])=O.C[Li].[CH3:14]COCC>C1COCC1>[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:3]=1[C:4](=[O:6])[CH3:14]
Reactant: CCOCC
Reactant: Cc1cccc(O)c1C(=O)O
Agent: [Li]C
Solvent: C1CCOC1
Product: CC(=O)c1c(C)cccc1O
Temperature: 60 °C
Reaction time: 6 h
Yield: 92.1 %

Procedure:
In a solution of 2-methoxy-6-methylbenzoic acid ethyl ester (5 g, 25.77 mmol) and NaOH (6.18 g, 154.64 mmol) in EtOH (100 mL) and water (40 mL) was stirred at reflux for 24 hours. EtOH was then removed using a rotary evaporator and the aqueous was acidified with HCl (1 N) to pH=4. Extract with CH2Cl2 (3×100 mL) followed by concentration using a rotary evaporator afforded 4.25 g of 2-methoxy-6-methylbenzoic acid (100%) as a white solid. To a solution of 2-methoxy-6-methylbenzoic acid (3.5 g, 21 mmol) in CH2Cl2 (100 mL) at room temperature was added BBr3 in CH2Cl2 (42 mL, 42 mmol). The reaction mixture was stirred at room temperature for 14 hrs and then concentrated using a rotary evaporator. The resulting residue was re-dissolved in CH2Cl2 (50 mL), diluted with HCl (0.5 N), extracted with CH2Cl2 (3×100 mL) and concentrated using a rotary evaporator to afford 3.3 g of 2-hydroxy-6-methylbenzoic acid (100%). To a solution of 2-hydroxy-6-methylbenzoic acid (3.3 g, 21.7 mmol) in THF (200 mL) at room temperature was slowly added CH3Li in ether (47 mL, 76 mmol) and the suspension was stirred at 60° C. for 6 hour. The reaction was quenched with HCl (0.5 N) aqueous and extracted with CH2Cl2 (3×100 mL). Concentration using a rotary evaporator afforded an oily residue. It was purified by column (SiO2, hexane/EtOAc=4:1) to provide 3 g of 2′-hydroxy-6′-methylacetophenone (92%) as a light yellow oil. A solution of 2′-hydroxy-6′-methylacetophenone (1.5 g, 10 mmol) in CH2Cl2 (50 mL) at room temperature was mixed with isonicotinoyl chloride hydrochloride (2.0 g, 11 mmol) and triethylamine (4.9 mL, 35 mmol) sequentially. The resulting mixture was stirred at room temperature for 14 hours, quenched with water, and extracted with CH2Cl2 (3×100 mL). Concentration using a rotary evaporator afforded a solid residue. It was purified by column (SiO2, hexane/EtOAc=3:1) to provide 1.5 g of the corresponding isonicotinic aryl ester (59%) as a light yellow solid. A solution of the above isonicotinic aryl ester (1.5 g, 5.88 mmol) in THF (100 mL) was mixed with potassium tert-butoxide (1.384 g, 12.35 mmol) and stirred at reflux for 2 hours. The reaction was quenched with water and acidified with HCl (0.5 N) to pH=6. Extract with CH2Cl2 (3×100 mL) followed by concentration using a rotary evaporator afforded a yellow solid residue. It was purified by column (SiO2, hexane/EtOAc=1:1) to provide 1.2 g of the diketone (80%). A solution of the above diketone (1.2 g, 24.71 mmol) in HOAc (100 mL) was stirred at reflux for 2 hours. All the solvent was removed using a rotary evaporator to afford a solid residue. It was then diluted with water and neutralized with NaOH (0.5 N) to pH=8. The solid was collected by filtration and washed with water and hexanes sequentially to afford 1 g of 5-methyl-2-(pyridin-4-yl)-4H-chromen-4-one as a light yellow solid (89%). A solution of 5-methyl-2-(pyridin-4-yl)-4H-chromen-4-one (0.85 g, 3.59 mmol) in dry carbon tetrachloride (250 mL) was mixed with NBS (0.67 g, 3.77 mmol) and benzyl peroxide (0.1 g, 0.422 mmol). The reaction mixture was stirred at reflux for 6 hours. After cooling the solvent was removed and the residue was further washed with hot water to get rid of succinimide. The solid was then purified by column (SiO2, hexanes/EtOAc=1:1) to yield 0.61 g of bromide (54%). A solution of the above bromide (0.61 g, 1.93 mmol) and NaOAc (1.82 g, 22.15 mmol) in HOAc (50 mL) was stirred at reflux for 6 hours. All the solvent was removed using a rotary evaporator to afford a solid residue. It was then diluted with water, extracted with CH2Cl2 (3×100 mL), and concentrated using a rotary evaporator. The solid was purified by column (SiO2, hexanes/EtOAc/MeOH=2:2:1) to yield 0.3 g of the corresponding acetate (53%). A solution of the above acetate (0.3 g, 1.01 mmol) and potassium carbonate (0.414 g, 3.0 mmol) in MeOH (30 mL) and water (3 mL) was stirred at room temperature for 48 hours. MeOH was removed using a rotary evaporator and the resulting mixture was further diluted with water (25 mL) to get a suspension. The solid was collected by filtration and washed with water and hexanes to yield 0.16 g of 5-hydroxymethyl intermediate (65%) as a light yellow solid. A suspension of the above intermediate (0.114 g, 0.45 mmol) in ethyl ether (10 mL) was mixed with HCl in ether (10 mL, 20 mmol) and the mixture was stirred at room temperature for 2 hours to get a even finer suspension. The solid was collected by filtration and washed with hexanes to yield 0.126 g of 5-(hydroxymethyl)-2-(pyridinyl)-4H-chromen-4-one (96%) as a light yellow solid.