Sodium Hydroxide → 6-[2-(3-Chloro-phenyl)-3-cyclopentyl-propionylamino]nicotinic acid

A solution of 6-[2-(3-chloro-phenyl)-3-cyclopentyl-propionylamino]-nicotinic acid methyl ester (146.9 mg, 0.38 mmol) in tetrahydrofuran/water/methanol (10 mL, 3:1:1) at 25° C. was treated with a 2N aqueous sodium hydroxide solution (0.4 mL, 0.80 mmol). The reaction mixture was stirred at 25° C. for 4 d. At this time, the reaction was concentrated in vacuo. The residue was diluted with water (50 mL) and extracted with diethyl ether (1×50 mL). The aqueous layer was acidified to pH=1 by the dropwise addition of a 3N aqueous hydrochloric acid solution. This solution was extracted with a solution of methylene chloride/methanol (3:1, 3×75 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was triturated with diethyl ether/hexanes (2:1) to afford 6-[2-(3-chloro-phenyl)-3-cyclopentyl-propionylamino]-nicotinic acid (63.6 mg, 44.4%) as a white solid: mp 251–255° C.; EI-HRMS m/e calcd for C20H21ClN2O3 (M+) 372.1240, found 372.1250.

1. concentrationAt this time, the reaction was concentrated in vacuo
2. additionThe residue was diluted with water (50 mL)
3. extractionextracted with diethyl ether (1×50 mL)
4. additionThe aqueous layer was acidified to pH=1 by the dropwise addition of a 3N aqueous hydrochloric acid solution
5. extractionThis solution was extracted with a solution of methylene chloride/methanol (3:1, 3×75 mL)
6. dry with materialThe combined organic layers were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe resulting solid was triturated with diethyl ether/hexanes (2:1)

ORD record

ord-24e4927b3f2744d698f8fceba2662530

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07223868B2