3,5-Dibromopyridine → Ethyl 3-(5-bromo-3-pyridinyl)-3-hydroxycyclopentanecarboxylate

A solution of THF:toluene (2.11 mL:2.11 mL) and n-BuLi (0.923 ml, 1.48 mmol) was cooled to −10° C. The reaction mixture was purged/filled with argon (3×). n-Butyl magnesium chloride (0.369 ml, 0.739 mmol) was added to the reaction mixture and stirred for 30 minutes. 3,5-Dibromopyridine (0.5 g, 2.111 mmol) was added to the reaction mixture over the course of 30 minutes, keeping bath below −10° C. and stirred for 1 hour. Ethyl 3-oxocyclopentanecarboxylate (0.330 g, 2.111 mmol) was added to the reaction mixture and stirred at −10° C. for ˜5 minutes. The reaction mixture was warmed to room temperature, diluted with saturated ammonium, extracted DCM (3×), and combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford ethyl 3-(5-bromopyridin-3-yl)-3-hydroxycyclopentanecarboxylate. MS ESI calc'd for C13H17BrNO3 [M+H]+ 314 and 316. found 314 and 316.

1. additionThe reaction mixture was purged/filled with argon (3×)
2. custombelow −10° C.
3. stirringstirred for 1 hour
4. stirringstirred at −10° C. for ˜5 minutes
5. extractionextracted DCM (3×)
6. concentrationwere concentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography (ethyl acetate/hexanes)

ORD record

ord-cb0b061e763b40f5b4e4d3790ad3b2e9

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376418B2