Diethyl Ether → HCID 67076147, compound

A solution of potassium bis(trimethylsilyl)amide (0.5 M in toluene, 31.5 mL) was added to an ice-bath cooled, stirred slurry of (methoxymethyl)triphenylphosphonium chloride (5.07 g) in tetrahydrofuran (50 mL) keeping the temperature of the reaction mixture below 10° C. The mixture was stirred for 30 min. A solution of 3-bromo-2-fluorobenzaldehyde (2 g) in THF (5+3 mL) was added dropwise and the cold bath was removed. The mixture was stirred at ambient temperature for 1.5 h. The mixture was quenched with saturated ammonium chloride solution and extracted into ethyl acetate (70 mL). The organic phase was washed with brine, dried over magnesium sulfate, filtered and evaporated to afford crude product. Ether (50 mL) was added and the mixture was left overnight in the fridge. The solid was filtered off and the filtrate was concentrated. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% ethyl acetate in isohexane to afford the subtitled compound (1.84 g) as a liquid. (5:3 mixture of isomers). 1H NMR (300 MHz, CDCl3) δ (a mixture of isomers) 7.98 (ddd, J=1.5, 7.1 and 8.4 Hz, 1H), 7.36-7.18 (m, 3H), 7.17 (d, J=13.1 Hz, 2H), 7.00-6.88 (m, 2H), 6.28 (d, J=7.1 Hz, 1H), 5.85 (d, J=13.1 Hz, 1H), 5.47 (d, J=7.1 Hz, 1H), 3.81 (d, J=6.5 Hz, 3H), 3.72 (d, J=6.5 Hz, 3H).

1. temperaturecooled
2. customthe temperature of the reaction mixture below 10° C
3. customthe cold bath was removed
4. stirringThe mixture was stirred at ambient temperature for 1.5 h
5. customThe mixture was quenched with saturated ammonium chloride solution
6. extractionextracted into ethyl acetate (70 mL)
7. washThe organic phase was washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customevaporated
11. customto afford crude product
12. waitthe mixture was left overnight in the fridge
13. filtrationThe solid was filtered off
14. concentrationthe filtrate was concentrated
15. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 20% ethyl acetate in isohexane

ORD record

ord-b3c6c65c164241c4a873a572c139a351

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017602B2