Sodium Hydroxide → (s)-3-[(1-Methoxypropan-2-yl)oxy]-5-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]benzoic acid

Participants

Reaction Steps

Triphenyl phosphine (21 g, 80 mmol, 2.8 equiv.) was added to a stirring solution of Methyl 3-hydroxy-5-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)benzoate (Intermediate 7) (9.3 g, 28.52 mmol, 1 equiv.) in toluene (100 mL) under nitrogen atmosphere at room temperature. The mixture was heated to 90° C. for 30 min. A mixture of Diisopropylazadicarboxylate (DIAD) (11.52 g, 57 mmol, 2 equiv.) and (R)-(−)-1-Methoxy-propan-2-ol (3.8 g, 42.8 mmol, 1.5 equiv.) in toluenene (50 mL) was added to the above reaction mixture at 90° C. and the reaction mixture was stirred for 3 h at 100° C. The completion of the reaction was monitored by TLC. After completion, the reaction mixture was concentrated under vacuum and purified by column chromatography to get (5)-Methyl 3-[(1-methoxypropan-2-yl)oxy]-5-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]benzoate (Intermediate 8) as thick liquid (27 g). Sodium hydroxide (3.43 g, 85.92 mmol, 3 equiv.) in water (55 mL) was added to a stirring solution of (9-Methyl 3-[(1-methoxypropan-2-yl)oxy]-5-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]benzoate (crude) (Intermediate 8) in methanol (110 mL) in round bottomed flask. The reaction mixture was stirred at room temperature for 2 h. The reaction was monitored by TLC. After completion, methanol was removed under vacuum and water was added. The reaction mixture was filtered. Filtrate was washed with ethyl acetate. The aqueous layer was acidified and extracted with DCM twice. The combined organic layer was washed with water, brine and dried over anhydrous sodium sulphate, filtered and concentrated in vacuum to furnish title acid as thick liquid (9.5 g).

Provenance & Evidence