Methyl iodide → 2-(4-Bromo-3-fluoro-2-methylphenoxy)tetrahydropyran

Temperature

-78 °C

2-(4-bromo-3-fluorophenoxy)tetrahydro-2H-pyran (1200 mg, 4.4 mmol) was dissolved in tetrahydrofuran (22 mL, 0.2M) under nitrogen and cooled to −78° C. To this was added (600 mg, 5.6 mmol) lithium diisopropylamide in solution dropwise over 5 minutes. The reaction mixture was stirred for 1 h at −78° C. Methyl iodide (948 mg, 6.5 mmol) was then added dropwise. The reaction was stirred at −78° C. for 30 min and allowed to warm to RT overnight. The mixture was quenched with water and 10 mL of saturated aqueous ammonium chloride solution. The reaction was extracted with diethyl ether (3×). The organic layer was dried over sodium sulfate, filtered and evaporated to yield 1.17 g (93%) of a light yellow mix of solid and oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.57-1.78 (m, 3H) 1.85-1.93 (m, 2H) 1.95-2.08 (m, 1H) 2.21 (d, J=2.34 Hz, 3H) 3.61 (m, J=11.27, 3.98, 3.98, 1.46 Hz, 1H) 3.78-3.88 (m, 1H) 5.41 (t, J=3.12 Hz, 1H) 6.81 (dd, J=8.98, 1.37 Hz, 1H) 7.27 (d, J=16.98 Hz, 1H)

1. stirringThe reaction was stirred at −78° C. for 30 min
2. temperatureto warm to RT overnight
3. customThe mixture was quenched with water and 10 mL of saturated aqueous ammonium chloride solution
4. extractionThe reaction was extracted with diethyl ether (3×)
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customto yield 1.17 g (93%) of a light
9. additionyellow mix of solid and oil

ORD record

ord-3afd8a4e195c4d9eb46576d8f3e3f2ae

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664401B2