Tributylamine → 3-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid ethyl ester

Temperature

90 °C

3-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid: To a mixture of 117A (956 mg, 4.00 mmol), 3,3-diethoxyprop-1-ene (1562 mg, 12.00 mmol), and Bu4NCl (1110 mg, 4.00 mmol) in DMF (22 mL) was added Bu3N (1480 mg, 8.00 mmol). To this mixture under N2 was added Pd(OAc)2 (26.9 mg, 0.12 mmol). The resulting mixture was stirred at 90° C. for 1.5 h, then cooled to rt and quenched with 2N HCl (10 mL). The resulting mixture was stirred for 20 min, then evaporated. The mixture was diluted with EtOAc, washed with water and brine, dried over MgSO4, and purified by flash chromatography to provide 3-(5-Methyl-2-tetrazol-1-yl-phenyl)-propionic acid ethyl ester (695 mg, 66.8%). LCMS m/z 261.2 (M+H)+. To a solution of this intermediate (690 mg, 2.65 mmol), in THF (10 mL) was added 2N LiOH (10 mL). The resulting mixture was stirred at rt for 3 h, then acidified to pH 3-4 with 2N HCl at 0° C. The mixture was concentrated and extracted with EtOAc (5×20 mL). The combined organic layers were washed with brine, dried over MgSO4, and purified by prep. HPLC to give 117B (567 mg, 92%). LCMS m/z 233.2 (M+H)+.

1. temperaturecooled to rt
2. customquenched with 2N HCl (10 mL)
3. stirringThe resulting mixture was stirred for 20 min
4. customevaporated
5. additionThe mixture was diluted with EtOAc
6. washwashed with water and brine
7. dry with materialdried over MgSO4
8. custompurified by flash chromatography

ORD record

ord-2793b045dbb04492a06312c17e14e888

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604056B2