2,4-DICHLOROPHENYLBUTYRIC ACID

3, 5-di-tert-butyl-4-methoxybenzaldehyde (1) A catalytic amount of AIBN was added to a solution of 1, 3-bis-(tert-butyl)-2-methoxy-5-methylbenzene (20d) (5 g, 21 mmol) and NBS (19 g, 106 mmol) in CCl (1) At first, sodium hydride (NaH, 1.27 g, 53 mmol) is added slowly into a solution of 3, 5-di-tert-butyl-4-hydroxybenzaldehyde (5 g, 21 mmol) dissolved in dry tetrahydrofuran (THF, 22.5 ml) at 0 C. under nitrogen. The mixture is removed from the cooling bath and the reaction proceeds for 30 min. Then, processes including adding methyl iodide (CH3I, 5.2 ml, 84 mmol) dissolved in dry THF (9 ml) in the mixture, refluxing for 12 hr, quenching with methanol (MeOH) in the cooling bath, extracting with dichloromethane (CH2Cl2), concentrating, purifying by a column chromatography method (using ethyl acetate:hexane=1:7 as eluent) are sequentially performed. A yellow liquid product (1) is obtained (4.5 g, 87%). 1H NMR (CDCl3, 400 MHz) delta 9.91 (s, 1H), 7.79 (s, 2H), 3.73 (s, 3H), 1.46 (s, 18H).A stirring mixture of 3, 5-di-tert-butyl-4-hydroxy-benzaldehyde (2 g, 8.53 mmol, 1 eq) in anhydrous THF (25 mL) was treated with NaH (853 mg, 21.34 mmol, 60%, 2.5 eq) at 0C under an argon atmosphere. The resulting mixture was stirred at 25 C for 30 min and then treated with Mel (7.7 g, 54.25 mmol, 3.38 mL, 6.36 eq) by dropwise addition. The resulting mixture was stirred at 85 C for 16 hr. The excess reagents were quenched by slow addition of brine (50 mL) and then extracted with Ethyl acetate (50 mL*3). The combined organic phase was washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by column chromatography (S1O2, Petroleum ether to Petroleum ether/Ethyl acetate=l0:l). The title compound (955 mg, 3.85 mmol, 45% yield) was obtained as yellow oil. 1 H NMR (CDCL, 400MHz) d = 9.91 (s, 1H), 7.79 (s, 2H), 3.73 (s, 3H), 1.45 (s, 18H).

Molecular Weight:233.09
XLogP3:3.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:232.0057849
Monoisotopic Mass:232.0057849
Topological Polar Surface Area:37.3
Heavy Atom Count:14
Complexity:208
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes