Dimethyl Sulfoxide → 3-Chloro-5-(trifluoromethoxy)benzaldehyde

Temperature

-78 °C

A solution of DMSO (16.1 g, 205.9 mmol) in anhydrous CH2Cl2 (300 mL) was cooled to −78° C. Oxalyl chloride (13.1 g, 103.0 mmol) was added slowly via a syringe (gas evolution was observed). The resulting solution was stirred at −78° C. for 15 minutes. A solution of 3-chloro-5-trifluoromethoxybenzyl alcohol (21.2 g, 93.6 mmol; see step (v) above) in CH2Cl2 (200 mL) was added via an addition funnel over a period of 15 minutes. The cloudy solution was stirred at −78° C. for 40 minutes and DIPEA (60.5 g, 468.0 mmol) was added via an addition funnel over 10 minutes. The resulting homogeneous solution was stirred at −78° C. for 1.5 hours, then warmed to room temperature and stirred 18 hours. The crude solution was concentrated in vacuo, the residue diluted with EtOAc and washed with H2O (1×), 2N HCl (1×), brine (1×), aqueous NaHCO3 (1×) and brine (1×). The organics were dried (Na2SO4), filtered and concentrated in vacuo to give the crude sub-title compound (19.9 g, 95%) which was used in the next step without further purification.

1. stirringThe cloudy solution was stirred at −78° C. for 40 minutes
2. stirringThe resulting homogeneous solution was stirred at −78° C. for 1.5 hours
3. temperaturewarmed to room temperature
4. stirringstirred 18 hours
5. concentrationThe crude solution was concentrated in vacuo
6. additionthe residue diluted with EtOAc
7. washwashed with H2O (1×), 2N HCl (1×), brine (1×), aqueous NaHCO3 (1×) and brine (1×)
8. dry with materialThe organics were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-98b858daf6a04997a9b3ffbb118e3870

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645751B2