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

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 TBF, 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 mmol) 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.

1. customto produce 8-1
2. additiona premixed
3. stirringThe resulting mixture was stirred for 18 hours at 70° C.
4. temperaturecooled
5. washwashed with water and brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. dissolutionTo the stirring residue dissolved in THF (400 mL)
9. additionwas added water (150 mL) and NaHCO3 (33 g)
10. waitafter 10 minutes
11. stirringAfter vigorous stirring for 30 minutes
12. additionthe mixture was diluted with ethyl acetate
13. washwashed with water and brine
14. dry with materialdried over MgSO4
15. concentrationconcentrated to an oil
16. customThe residue was chromatographed on silica gel (10-20% EtOAc/hexane)

ORD record

ord-985f3df930b2455887134671793b4187

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06693101B2