1,2-Dichloroethane → HCID 58229473, compound

A dry, 100 mL one neck round bottom flask was charged with 5-bromo-2-iodopyridin-3-ol (2.30 g, 7.67 mmol), 15 mL dry THF, a stirbar and n,n-diisopropylethylamine, 99.5% (1.74 ml, 9.97 mmol). The flask was fitted with an inert atmosphere inlet, and swept with Ar for several minutes. To the stirring solution was added 2-methoxyethoxymethyl chloride (0.955 ml, 8.44 mmol) over 5 minutes. The reaction was stirred at room temperature for 24 h, and poured onto 100 mL DCE. The solution as washed with 5% NaHCO3 (2×25 mL) and the DCE solution was passed through an unbuffered Varian Chem elute CE1010 (100 mL, PN 12198010). The tube was extracted with DCE (2×40 mL), and the combined DCE solution was concentrated in vacuo. The residue was purified using 80 g of SiO2 wet packed with 5% THF in hexanes and eluted with 500 mL 10% THF, followed by 500 mL 15% THF in hexanes. A band that eluted with Rf=0.33 (15% THF in hexanes) was isolated. The solvent was removed in vacuo to afford 5-bromo-2-iodo-3-((2-methoxyethoxy)methoxy)pyridine as the major component of a 70:30 mixture with 5-bromo-2-chloro-3-((2-methoxyethoxy)methoxy)pyridine (2.0846 g). Data for 5-bromo-2-iodo-3-((2-methoxyethoxy)methoxy)pyridine: 1H NMR (300 MHz, chloroform-d) δ ppm 3.38 (s, 3H) 3.57 (dd, J=6.43, 2.70 Hz, 1H) 3.57 (t, J=4.46 Hz, 1H) 3.87 (ddd, J=6.34, 2.76, 1.94 Hz, 2H) 5.36 (s, 2H) 7.50 (d, J=2.05 Hz, 1H) 8.14 (d, J=2.05 Hz, 1H). 13C NMR (75 MHz, chloroform-d) δ ppm 59.04 (s, 1 C) 68.53 (s, 1 C) 71.28 (s, 1 C) 94.17 (s, 1 C) 110.02 (s, 1 C) 120.28 (s, 1 C) 124.12 (s, 1 C) 144.61 (s, 1 C) 153.67 (s, 1 C). NMR data for 5-bromo-2-chloro-3-((2-methoxyethoxy)methoxy)pyridine: 1H NMR (300 MHz, chloroform-d) δ ppm 3.38 (s, 3H) 3.57 (dd, J=6.43, 2.70 Hz, 1H) 3.57 (t, J=4.46 Hz, 1H) 3.87 (ddd, J=6.34, 2.76, 1.94 Hz, 2H) 5.36 (s, 2H) 7.71 (d, J=2.12 Hz, 1H) 8.12 (d, J=2.12 Hz, 1H). 13C NMR (75 MHz, chloroform-d) δ ppm 59.04 (s, 1 C) 68.53 (s, 1 C) 71.28 (s, 1 C) 94.24 (s, 1 C) 118.90 (s, 1 C) 126.44 (s, 1 C) 140.18 (s, 1 C) 142.57 (s, 1 C) 149.75 (s, 1 C).

1. customThe flask was fitted with an inert atmosphere inlet
2. waitswept with Ar for several minutes
3. washThe solution as washed with 5% NaHCO3 (2×25 mL)
4. washelute CE1010 (100 mL, PN 12198010)
5. extractionThe tube was extracted with DCE (2×40 mL)
6. concentrationthe combined DCE solution was concentrated in vacuo
7. customThe residue was purified
8. washeluted with 500 mL 10% THF
9. washA band that eluted with Rf=0.33 (15% THF in hexanes)
10. customwas isolated
11. customThe solvent was removed in vacuo

ORD record

ord-649ab7e361494e20bd42cfe43e3f41e8

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928140B2