Dimethyl Sulfide → HCID 89463002, compound

Phenyl chloroformate (4.2 mL, 0.033 mol) was added to a mixture of 3-bromo-5-fluoro-pyridine (5.5 g, 0.031 mol), dimethyl sulphide (15.32 mL, 0.209 mol) and copper iodide (5.95 g, 0.031 mol) in anhydrous tetrahydrofuran (50 mL) at RT and the reaction mixture was stirred for 40-50 min. To this suspension, cyclopropylmagnesiumbromide (66.75 mL, 0.033 mol, 0.5 M solution in tetrahydrofuran) was added at −25 to −20° C. over a 30-40 min period. The mixture was stirred at this temperature for 30 min, and then warmed slowly to RT over 1.0-1.5 hrs. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution (200 mL), followed by extraction of the aqueous layer with ethyl acetate (3×200 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (2×100 mL), and dried over anhydrous sodium sulphate to afford the crude compound, which was purified by silica gel chromatography using 0-5% ethyl acetate-hexane gradient. This yielded crude phenyl 3-bromo-4-cyclopropyl-5-fluoro-4H-pyridine-1-carboxylic acid phenyl ester.

1. stirringThe mixture was stirred at this temperature for 30 min
2. customThe reaction mixture was quenched with a saturated aqueous ammonium chloride solution (200 mL)
3. extractionfollowed by extraction of the aqueous layer with ethyl acetate (3×200 mL)
4. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (2×100 mL)
5. dry with materialdried over anhydrous sodium sulphate
6. customto afford the crude compound, which
7. customwas purified by silica gel chromatography

ORD record

ord-cc5084c651f34f908a3e5e9ce1bb2f5e

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193724B2