2-Bromo-6-(1,3-dioxolan-2-yl)pyridine → 2-Cyclopropyl-6-(1,3-dioxolan-2-yl)pyridine

To a stirred solution of 0.5 M zinc chloride in THF (9.1 mL, 4.55 mmol) under N2, cooled to −78° C. was added dropwise a solution of 0.5 M cyclopropylmagnesium bromide in THF (9.1 mL, 4.55 mmol). The reaction mixture was warmed to RT and stirred for 1 h. The resulting zincate was transferred via syringe to a sealed tube containing a solution of 2-bromo-6-(1,3-dioxolan-2-yl)pyridine of Step B (694.3 mg, 3.03 mmol) and Pd(PPh3)4 in dry THF (3 mL). The reaction mixture was degassed, sealed and heated at 120° C. for 2 h. The reaction mixture was cooled to RT and partitioned between ethyl acetate (100 mL) and saturated aqueous NH4Cl (50 mL). The phases were separated. The aqueous phase was extracted with ethyl acetate (15 mL). The combined organic phases were dried (MgSO4), filtered and concentrated. The resulting residue was dissolved in CH2Cl2, adsorbed onto silica gel and purified on a Biotage 40S column with SIM using 10% ethyl acetate in hexane as the eluent to afford 538.2 mg (2.82 mmol, 93%) of the desired product as a bright yellow liquid.

1. customThe reaction mixture was degassed
2. customsealed
3. temperatureheated at 120° C. for 2 h
4. temperatureThe reaction mixture was cooled to RT
5. custompartitioned between ethyl acetate (100 mL) and saturated aqueous NH4Cl (50 mL)
6. customThe phases were separated
7. extractionThe aqueous phase was extracted with ethyl acetate (15 mL)
8. dry with materialThe combined organic phases were dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe resulting residue was dissolved in CH2Cl2
12. custompurified on a Biotage 40S column with SIM

ORD record

ord-9ea9c2e04e89462394c3858924ada901

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417041B2