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

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).

1. customAfter completion, methanol was removed under vacuum and water
2. additionwas added
3. filtrationThe reaction mixture was filtered
4. washFiltrate was washed with ethyl acetate
5. extractionextracted with DCM twice
6. washThe combined organic layer was washed with water, brine
7. dry with materialdried over anhydrous sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated in vacuum

ORD record

ord-0900d8259bd448e9b863d32542be87c5

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450494B2