Acetic Acid → 3-[(2S)-1-(Difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoic acid

Temperature

0 °C

To methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-benzoate (76.3 g, 179 mmol) was added NMP (534 mL), water (305 mL) and the solution was stirred at 0° C. 2N sodium hydroxide (152 mL, 305 mmol) was charged dropwise and the reaction stirred for 4 hours. Acetic acid (41 mL, 718 mmol) was charged dropwise followed by water (1068 mL) and 1N HCl (400 mL) was added until pH 3 was reached and some material oiled out. The aqueous layer was extracted with toluene (3×988 mL) and combined with the material that oiled out which was dissolved in ethyl acetate (988 mL) and the combined organic layers were washed with water (988 mL), saturated aqueous brine (988 mL), dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography eluting with 5% MeOH in dichloromethane to afford the title compound (64 g).

1. stirringthe reaction stirred for 4 hours
2. additionwas added until pH 3
3. extractionThe aqueous layer was extracted with toluene (3×988 mL)
4. dissolutionwas dissolved in ethyl acetate (988 mL)
5. washthe combined organic layers were washed with water (988 mL), saturated aqueous brine (988 mL)
6. dry with materialdried (MgSO4)
7. customevaporated under reduced pressure
8. customThe residue was purified by flash chromatography
9. washeluting with 5% MeOH in dichloromethane

ORD record

ord-c7f4ae0399d141379a30bcd864ad2295

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07964725B2