AKOS B030638 synthesis

Yield:70442-56-7 100%

Reaction Conditions:

Stage #1: 4-(2,3-dimethylphenoxy)butyric acid ethyl esterwith lithium hydroxide in 1,4-dioxane at 60; for 4 h;
Stage #2: with hydrogenchloride in 1,4-dioxane at 20; pH=2 - 3;

Steps:

1.D

Step D. 4-(2,3-Dimethylphenoxy)butanoic acid [00140] A mixture of ethyl 4-(2,3-dimethylphenoxy)butanoate (22.28 g, 94 mmol), 4 N LiOH (94 mL, 377 mmol) in dioxane (50 mL) was heated at 60 °C for 4 h. After cooling to room temperature, the mixture was adjusted to pH 2-3 with 3 N HC1, and extracted with EtOAc (2x10 mL). The combined organic phases were washed with brine, dried over anhydrous a2S0₄, filtered, and concentrated to afford the title compound (20 g, 100% yield). LCMS, [M-H]⁺ = 207.1. 'H NMR (400 MHz, CDC1₃) δ 7.02 (dd, J= 8.2, 7.5 Hz, 1H), 6.76 (d, J= 7.5 Hz, 1H), 6.67 (d, J= 8.2 Hz, 1H), 3.99 (t, J= 6.0 Hz, 2H), 2.60 (t, J= 7.3 Hz, 2H), 2.25 (s, 3H), 2.18 - 2.09 (m, 2H), 2.12 (s, 3H).

References:

WO2012/149236,2012,A1 Location in patent:Page/Page column 90-91