4-Methylmorpholine → N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{(3-(1H-tetrazol-1-yl)-phenyl]oxy}acetamide

To a 25 mL recovery flask was added 3-tetrazol-1-ylphenoxyacetic acid 3 (200 mg, 0.908 mmol, 1.0 eq.) and a stirbar. 1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (261 mg, 1.36 mmol, 1.5 eq.) and 1-hydroxybenzotriazole (184 mg, 1.36 mmol, 1.5 eq.) were added to the flask. DMF (10 mL) and N-methylmorpholine (300 μL, 2.72 mmol, 3.0 eq.) were added to the reaction flask. The mixture was allowed to stir for 30 min at room temperature. 5-amino-2-chlorobenzotrifluoride (355 mg, 1.82 mmol, 2.0 eq.) was added to the flask and the resulting mixture was allowed to stir overnight at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL), and sat'd aq. NaCl (1×50 mL). The aqueous phases were combined and extracted with ethyl acetate (2×30 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated to yield an off-white solid, which did not require further purification (165 mg, 46%). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 398.0 (M+H)+1 1H-NMR, Varian 400 MHz (DMSO-d6) δ 10.55 (bs, 1H), 10.09 (s, 1H), 8.22 (d, 1H), 7.93-7.91 (m, 1H), 7.68 (d, 1H), 7.61-7.51 (m, 3H), 7.21-7.18 (m, 1H), 4.88 (s, 2H) ppm.

1. stirringto stir overnight at room temperature
2. washwashed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL)
3. extractionextracted with ethyl acetate (2×30 mL)
4. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield an off-white solid, which
8. custompurification (165 mg, 46%)

ORD record

ord-3cd356782e1548c8b29e58a21cb16aa0

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362017B2