2,5-Dibromopyridine → HCID 57803252, compound

Temperature

-78 °C

To a solution of 2,5-dibromopyridine (4.10 g, 17 mmol) in anhydrous toluene (250 mL) at −78° C. was dropwise added n-BuLi (1.6 M, 12 mL). After stirred at −78° C. for 2.5 hours, a solution of 1,4-dioxa-spiro[4.5]decan-8-one (2.73 g, 17 mmol) in methylene chloride (25 mL) was added into the reaction mixture, and the resulting mixture was stirred for additional one hour and allowed to warm up to rt slowly. The reaction mixture was poured into aqueous NaHCO3 (200 mL) and then extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with saline solution (2×50 mL), dried over MgSO4, concentrated in vacuo. The resulting solid was titrated with ether and the filtrate was collected. The ether was removed and the solid was chromatographed on silica gel, eluting with hexane/ethyl acetate (2 to 1), to give 8-(5-bromopyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol (4.27 g) as pale yellow solid. LCMS: 316.10/314.10 (M+H+, 100%). 1H NMR: δ 8.6 (s, 1 H), 7.82 (d, 1 H), 7.38 (d, 1 H), 4.6 (s, 1 H), 4.0 (m, 4 H), 2.2 (m, 4 H), 1.7 (m, 4 H).

1. customat −78° C.
2. stirringthe resulting mixture was stirred for additional one hour
3. temperatureto warm up to rt slowly
4. extractionextracted with EtOAc (2×50 mL)
5. washwashed with saline solution (2×50 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. customthe filtrate was collected
9. customThe ether was removed
10. customthe solid was chromatographed on silica gel
11. washeluting with hexane/ethyl acetate (2 to 1)

ORD record

ord-498a12d5f706420eaedb72f6f20e3f8c

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729063B2