Oxalyl chloride → 5,6-Difluoro-1-indanone

To a solution of 3,4-difluorocinnamic acid (5.0 g, 26.9 mmol) in DCM (35 mL) at 0° C., was added DMF (1 drop) and oxalyl chloride (4.7 mL, 53.8 mmol). The reaction mixture was warmed to rt and stirred for 16 h. The solvents were removed in vacuo and the residue azeotroped with toluene (2×20 mL). The residue was redissolved in carbon disulfide (20 mL) and added to a solution of aluminum trichloride (12.4 g, 94.1 mmol) in carbon disulfide (50 mL) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, heated to reflux for 4 h and then cooled to rt. The reaction mixture was poured into ice, extracted with EtOAc (2×500 mL) and the combined organic phase dried (MgSO4). Solvent was removed in vacuo and the residue purified by column chromatography (EtOAc:isohexane 1:9) to give the title compound: δH (CDCl3) 2.73 (2H, t), 3.17 (2H, t), 7.32 (1H, t), 7.43 (1H, t).

1. customThe solvents were removed in vacuo
2. customthe residue azeotroped with toluene (2×20 mL)
3. dissolutionThe residue was redissolved in carbon disulfide (20 mL)
4. stirringThe reaction mixture was stirred at 0° C. for 30 min
5. temperatureheated
6. temperatureto reflux for 4 h
7. temperaturecooled to rt
8. additionThe reaction mixture was poured into ice
9. extractionextracted with EtOAc (2×500 mL)
10. dry with materialthe combined organic phase dried (MgSO4)
11. customSolvent was removed in vacuo
12. customthe residue purified by column chromatography (EtOAc:isohexane 1:9)

ORD record

ord-9a31cff8243a428f9a608942dcf9f765

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278442B2