2-Chloro-3-nitrobenzaldehyde → HCID 57937549, compound

Temperature

-40 °C

To ether cooled to −78° C. was added titanium (IV) chloride (0.85 mL, 7.8 mmol) and a 1.6M solution of methyl lithium in ether (4.9 ml, 7.8 mmol). After warming the mixture to −40° C., it was transferred via double-tipped needle to a −78° C. ether solution of 2-chloro-3-nitrobenzaldehyde (1.0 g, 5.6 mmol), which can be synthesized according to the procedure in J. Med. Chem. 1088, 31, 936-944. The reaction was allowed to slowly warm to rt and was quenched with the addition of MeOH and water. The layers were separated, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4 and concentrated to an oil. The crude material was purified by flash column chromatography (10% EtOAc:hexanes) to give 0.98 g of the racemic compound (84%). The enantiomers were separated using packed column supercritical fluid chromatography (SFC) on a 3×25 cm Dalcel® AD-H column with a 90 g/min total flow (81 q/min CO2-90%) (9 g/min MeOH-10%) to give the title compound as a yellow oil. 1H NMR (400 MHz, d6-DMSO) δ 7.86 (m, 1H), 7.58 (m, 1H), 5.62 (d, J=4.4 Hz, 1H), 5.06 (m, 1H), 1.30 (d, J=6.4 Hz, 3H).

1. customwas transferred via double-tipped needle to a −78° C.
2. customcan be synthesized
3. temperatureto slowly warm to rt
4. customwas quenched with the addition of MeOH and water
5. customThe layers were separated
6. extractionthe aqueous phase was extracted with EtOAc
7. washThe combined organic phases were washed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated to an oil
10. customThe crude material was purified by flash column chromatography (10% EtOAc:hexanes)

ORD record

ord-af5be3b87a4a4ce3bfac525002ba4698

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07615643B2