4-Chloro-2-fluorobenzaldehyde → HCID 21617990, compound

Temperature

15 °C

A solution of KOt-Bu (19.5 g, 174 mmol) in dry THF (300 mL) was cooled with an ice/water bath. Portionwise addition of MePPh3Br (62.2 g, 174 mmol) resulted in a suspension, which was stirred for 5 min at 0° C. and for 1 h at 15° C. Subsequently, the temperature was lowered to 0° C. and a solution of 4-chloro-2-fluorobenzaldehyde (25.1 g, 158 mmol) in dry THF (100 mL) was added dropwise. The temperature was raised to room temperature slowly. The reaction mixture was stirred at room temperature for 20 h. Addition of brine (100 mL) resulted in a clear two phase system and a white solid. The combination of layers was decanted from the solid. The layers were separated, the aqueous layer was combined with the solid residue and Et2O (200 mL). The combination of layers was decanted from the solid. The layers were separated, the combination of organic layers was dried (Na2SO4) and concentrated at a controlled vacuum of 100 mbar. The residual oil was combined with pentane (300 mL) and Na2SO4. The suspension was triturated. Filtration and pentane washing provided a filtrate, which was concentrated at a controlled vacuum of 100 mbar to arrive at 26.76 g (97%, 90% purity) of impure title compound as a yellow oil.

1. additionPortionwise addition of MePPh3Br (62.2 g, 174 mmol)
2. customresulted in a suspension, which
3. customwas lowered to 0° C.
4. temperatureThe temperature was raised to room temperature slowly
5. stirringThe reaction mixture was stirred at room temperature for 20 h
6. customresulted in a clear two phase system
7. customThe combination of layers was decanted from the solid
8. customThe layers were separated
9. customThe combination of layers was decanted from the solid
10. customThe layers were separated
11. dry with materialthe combination of organic layers was dried (Na2SO4)
12. concentrationconcentrated at a controlled vacuum of 100 mbar
13. customThe suspension was triturated
14. filtrationFiltration and pentane washing
15. customprovided a filtrate, which
16. concentrationwas concentrated at a controlled vacuum of 100 mbar

ORD record

ord-b975de64a0a54a11b03ad08e0ec27611

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09302988B2