2-FLUORO-5-METHOXYBENZOICACID

Class white powder

To a solution of 1 -fluoro-4-methoxy-benzene (5 g, 39.6 mmol, 1.0 eq) and PMDTA (7.56 g, 43.62 mmol, 1.leq) in dry THF (100 mL) at -60 °C under NTo a vigorously stirred mixture [OF 4-FLUORO-3-METHYLANISOLE] (12.0 g, 85.6 mmol) and pyri- dine (41.7 g, 527 mmol) in water (170 mL) at [50°C] was added portion-wise potassium per- manganate (44.65 g, mmol) and then maintained at this temperature for 2 h. The resulting mixture was then allowed to cool to RT and allowed to stand overnight and then heated for a further 5 h at [50°C.] Then the mixture was filtered over celite and then the residue was washed with sulfuric acid (conc. 100 mL). The combined filtrates were then [HALF-EVAPORA-] ted and neutralised with potasssium carbonate. Then the mixture was washed with diethyl ether and then the aqueous layer was acidified with hydrochloric acid (conc.) and the pro- duct extracted with diethyl ether. The combined extracts were then dried over sodium sul- phate. After filtration and evaporation the crude solid was [RECRYSTALLISED] from 1, 2, -di- chloroethane to afford the title compound (4.4 g, 30percent) as a light pink solid. MS [M/E =] 168.9 (M-H). Alternatively, a solution of 4-fluoroanisole (500 mg, 4.0 mmol) in THF (10 mL) was added to a cooled [SOLUTION (-78°C) OF 2, ] 2, 6, 6-tetramethylpiperidine (1.1 g, 7.9 mmol) and BuLi (5 mL, 1.6 M in hexanes, 7.9 mmol) in THF (10 mL) at a slow rate to maintain the tempera- ture [BELOW-70°C.] The mixture was maintained at this temperature for 12 h, and then dry C02 gas was passed into the solution. The resulting mixture was allowed to warm up to 0°C and then HCl (1 M, 10 mL) was added and the product was extracted with diethyl ether. The combined organic extracts were then dried over sodium sulfate, washed with water and brine, filtered and evaporated. The crude solid was then partioned between sodium hydroxide [(1] M, 10 mL) and diethyl ether. The aqueous phase was then acidified with HCl (1 M) and the product extracted with diethyl ether. Evaporation afforded the title compound (268 mg, 40percent) as a white solid. MS m/e = 168.9 (M-H).To a vigorously stirred mixture [OF 4-FLUORO-3-METHYLANISOLE] (12.0 g, 85.6 mmol) and pyri- dine (41.7 g, 527 mmol) in water (170 mL) at [50°C] was added portion-wise potassium per- manganate (44.65 g, mmol) and then maintained at this temperature for 2 h. The resulting mixture was then allowed to cool to RT and allowed to stand overnight and then heated for a further 5 h at [50°C.] Then the mixture was filtered over celite and then the residue was washed with sulfuric acid (conc. 100 mL). The combined filtrates were then [HALF-EVAPORA-] ted and neutralised with potasssium carbonate. Then the mixture was washed with diethyl ether and then the aqueous layer was acidified with hydrochloric acid (conc.) and the pro- duct extracted with diethyl ether. The combined extracts were then dried over sodium sul- phate. After filtration and evaporation the crude solid was [RECRYSTALLISED] from 1, 2, -di- chloroethane to afford the title compound (4.4 g, 30percent) as a light pink solid. MS [M/E =] 168.9 (M-H). Alternatively, a solution of 4-fluoroanisole (500 mg, 4.0 mmol) in THF (10 mL) was added to a cooled [SOLUTION (-78°C) OF 2, ] 2, 6, 6-tetramethylpiperidine (1.1 g, 7.9 mmol) and BuLi (5 mL, 1.6 M in hexanes, 7.9 mmol) in THF (10 mL) at a slow rate to maintain the tempera- ture [BELOW-70°C.] The mixture was maintained at this temperature for 12 h, and then dry C02 gas was passed into the solution. The resulting mixture was allowed to warm up to 0°C and then HCl (1 M, 10 mL) was added and the product was extracted with diethyl ether. The combined organic extracts were then dried over sodium sulfate, washed with water and brine, filtered and evaporated. The crude solid was then partioned between sodium hydroxide [(1] M, 10 mL) and diethyl ether. The aqueous phase was then acidified with HCl (1 M) and the product extracted with diethyl ether. Evaporation afforded the title compound (268 mg, 40percent) as a white solid. MS m/e = 168.9 (M-H).To a solution of

Molecular Weight:170.14
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:170.03792224
Monoisotopic Mass:170.03792224
Topological Polar Surface Area:46.5
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes