Propargyl bromide → 2-Cyclopropyl-1-methoxy-4-nitrobenzene

Temperature

65 °C

To a 0.5M 9-BBN/THF solution (26.0 mL, 13.0 mmol) was added propargyl bromide (0.71 mL, 6.37 mmol, 80% in toluene) and the mixture was heated at 65° C. for 5 h. After cooling to 20° C., a previously degassed solution of NaOH (749 mg, 18.7 mmol) in water (6.3 mL) was added and stirring was continued for 1.5 h. The mixture was transferred to a second flask containing 2-bromo-4-nitroanisole (1.29 g, 5.45 mmol) and tetrakis(triphenylphosphine)palladium (0) (187 mg, 0.16 mmol) in THF (8.0 mL). After heating at 60° C. for 14 h, the reaction mixture was quenched with water (15 mL) and extracted with ether (3×40 mL). The combined organic extracts wee washed with 2M NaOH (3×20 mL) and water (3×20 mL), dried (Na2SO4) and concentrated. Purification by two consecutive column chromatographies (SiO2, 1st eluting with 9/1 hexanes/EtOAc, 2nd eluting with 7/3 hexanes/CH2Cl2) allowed to isolate the title compound (113 mg, 11% yield) as a yellowish oil: LCMS (ES) m/z 194 (M+H).

1. temperatureAfter cooling to 20° C.
2. customThe mixture was transferred to a second flask
3. temperatureAfter heating at 60° C. for 14 h
4. customthe reaction mixture was quenched with water (15 mL)
5. extractionextracted with ether (3×40 mL)
6. washThe combined organic extracts wee washed with 2M NaOH (3×20 mL) and water (3×20 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. customPurification
10. washby two consecutive column chromatographies (SiO2, 1st eluting with 9/1 hexanes/EtOAc, 2nd eluting with 7/3 hexanes/CH2Cl2)

ORD record

ord-f6180b295a774b9a96a5f4779db726e1

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618115B2