Sodium Hydroxide → 4-[(1S)-1-[[(2R)-3-methyl-2-(2-phenoxyethoxy)butanoyl]amino]ethyl]benzoic acid

Temperature

55 °C

To a solution of methyl 4-[(1S)-1-[[(2R)-3-methyl-2-(2-phenoxyethoxy)butanoyl]amino]ethyl]benzoate (30 g, 75.1 mmol) in THF (300 mL) is added 2N NaOH (94 mL, 188 mmol). The mixture is stirred at 55° C. overnight, cooled, and concentrated to remove THF. The aqueous residue is diluted with water (200 mL) and extracted with ethyl acetate (2×200 mL). The organic layers are discarded. The aqueous layer is acidified to pH 2 using conc. HCl (25 mL) and extracted with ethyl acetate (2×200 mL). The combined ethyl acetate layers are dried with MgSO4, filtered, and concentrated. The material is slurried with heptane (500 mL) at 60° C. for 2 h, cooled to room temperature, and filtered. The resulting solid is slurried with water (500 mL) at 60° C. for 2 h, cooled to room temperature, filtered, and dried at 40° C. to provide the title compound as a white solid (20 g, 69%). MS (m/z): 386.0 (M+1).

1. temperaturecooled
2. concentrationconcentrated
3. customto remove THF
4. additionThe aqueous residue is diluted with water (200 mL)
5. extractionextracted with ethyl acetate (2×200 mL)
6. extractionextracted with ethyl acetate (2×200 mL)
7. dry with materialThe combined ethyl acetate layers are dried with MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. waitThe material is slurried with heptane (500 mL) at 60° C. for 2 h
11. temperaturecooled to room temperature
12. filtrationfiltered
13. waitThe resulting solid is slurried with water (500 mL) at 60° C. for 2 h
14. temperaturecooled to room temperature
15. filtrationfiltered
16. customdried at 40° C.

ORD record

ord-30650d477cef4fa8b668def72f8298f9

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000043B2