Tetrahydrofuran → 5-(5-Bromo-pyridin-2-yl)-pentanoic acid ethyl ester

Participants

Reaction Steps

To a stirred solution of ethyl-1-pentenoic acid (10 g, 78 mmol) in degassed THF (80 mL) at 0° C. was added dropwise a solution of 9-BBN (187 mL of 0.5 M in THF, 94 mmol) and the mixture stirred for 18 hours at ambient temperature to produce 8-1. K2CO3 (18.4 g, 133 mmol) and 2,5-dibromopyridine (18.5 g, 78 mmol) were added, followed by a premixed and aged (70° C. for 30 min) suspension of Pd(OAc)2 (2.0 g, 8.9 mmol) and DPPF (5.4 g, 9.8 m-mol) in degassed DMF (80 mL). The resulting mixture was stirred for 18 hours at 70° C., cooled, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated. To the stirring residue dissolved in THF (400 mL) was added water (150 mL) and NaHCO3 (33 g) and after 10 minutes, NaBO3.H2O (48 g). After vigorous stirring for 30 minutes, the mixture was diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated to an oil. The residue was chromatographed on silica gel (10–20% EtOAc/hexane) to give 8-2 as a colorless oil.

Provenance & Evidence