Oxalyl chloride → 6-Fluoro-4-methylindan-1-one

To a solution of 3-(4-fluoro-2-methylphenyl)propanoic acid (12 g, 65.93 mmol) in CH2Cl2 (200 mL) was added oxalyl chloride (11.3 mL, 131.7 mmol) and stirred at RT for 16 h. The reaction mixture was concentrated in vacuo and re-dissolved in CH2Cl2 (150 mL) and added to a suspension of AlCl3 (11.4 g, 85.7 mmol) in CH2Cl2 (150 mL) at 0° C. The reaction mixture was heated at 50° C. for 3 h and allowed to stir at RT for 16 h. The reaction mixture poured into ice water (150 mL), extracted with CH2Cl2 (2×100 mL), the organic extract was washed with 1N NaOH solution (2×50 mL), brine solution (50 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by silica gel column chromatography, eluting with 10% EtOAc/petroleum ether 60-80 to afford 6-fluoro-4-methyl-2,3-dihydro-1H-inden-1-one as an off white solid (7 g, 70%).

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionre-dissolved in CH2Cl2 (150 mL)
3. temperatureThe reaction mixture was heated at 50° C. for 3 h
4. stirringto stir at RT for 16 h
5. extractionextracted with CH2Cl2 (2×100 mL)
6. extractionthe organic extract
7. washwas washed with 1N NaOH solution (2×50 mL), brine solution (50 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude material was purified by silica gel column chromatography
11. washeluting with 10% EtOAc/petroleum ether 60-80

ORD record

ord-6e45e9774b564442b891233dca959d38

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193689B2